{"entity": "researcher", "timestamp": "2026-06-08T10:59:41.280Z", "family": "Eriksson", "given": "Jens", "initials": "J", "orcid": "0000-0002-8945-2665", "affiliations": ["Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 75123 Uppsala, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe04815d524b48c2ba80c094c629362f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe04815d524b48c2ba80c094c629362f"}}, "publications": [{"entity": "publication", "iuid": "2d6d03aaf58242b6b95f18bddc3092a8", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2d6d03aaf58242b6b95f18bddc3092a8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2d6d03aaf58242b6b95f18bddc3092a8"}}, "title": "A two-step activation mechanism enables mast cells to differentiate their response between extracellular and invasive enterobacterial infection.", "authors": [{"family": "von Beek", "given": "Christopher", "initials": "C", "orcid": "0000-0001-6310-7583", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fba39ea4c0f74e65a1a61e1ad1fb7b73.json"}}, {"family": "Fahlgren", "given": "Anna", "initials": "A"}, {"family": "Geiser", "given": "Petra", "initials": "P", "orcid": "0000-0003-2785-4201", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0487e44d013c4faea6523a9f4b23cbe6.json"}}, {"family": "Di Martino", "given": "Maria Letizia", "initials": "ML", "orcid": "0000-0002-9491-4000", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ccaa06e9e2d441589299b7e33ee55034.json"}}, {"family": "Lindahl", "given": "Otto", "initials": "O", "orcid": "0000-0001-7518-9483", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9438c537a23642f5b5269f3428b2b9f8.json"}}, {"family": "Prensa", "given": "Grisna I", "initials": "GI", "orcid": "0009-0002-7101-7224", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e90e9ea8e5924e219ceb2fdfd9c6c113.json"}}, {"family": "Mendez-Enriquez", "given": "Erika", "initials": "E", "orcid": "0000-0002-2114-2812", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4ab7409b0b124890a689f4b7b1cc06db.json"}}, {"family": "Eriksson", "given": "Jens", "initials": "J", "orcid": "0000-0002-8945-2665", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe04815d524b48c2ba80c094c629362f.json"}}, {"family": "Hallgren", "given": "Jenny", "initials": "J", "orcid": "0000-0002-3685-5364", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6c9f67368cbc4ebd929f38f4bca9da03.json"}}, {"family": "F\u00e4llman", "given": "Maria", "initials": "M", "orcid": "0000-0001-6874-6384", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e36dc965299248a5a309013213e2fb44.json"}}, {"family": "Pejler", "given": "Gunnar", "initials": "G"}, {"family": "Sellin", "given": "Mikael E", "initials": "ME", "orcid": "0000-0002-8355-0803", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/559c18ec87d64318a0afc6267ea879e2.json"}}], "type": "journal article", "published": "2024-01-30", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "904", "issn-l": "2041-1723"}, "abstract": "Mast cells localize to mucosal tissues and contribute to innate immune defense against infection. How mast cells sense, differentiate between, and respond to bacterial pathogens remains a topic of ongoing debate. Using the prototype enteropathogen Salmonella Typhimurium (S.Tm) and other related enterobacteria, here we show that mast cells can regulate their cytokine secretion response to distinguish between extracellular and invasive bacterial infection. Tissue-invasive S.Tm and mast cells colocalize in the mouse gut during acute Salmonella infection. Toll-like Receptor 4 (TLR4) sensing of extracellular S.Tm, or pure lipopolysaccharide, causes a modest induction of cytokine transcripts and proteins, including IL-6, IL-13, and TNF. By contrast, type-III-secretion-system-1 (TTSS-1)-dependent S.Tm invasion of both mouse and human mast cells triggers rapid and potent inflammatory gene expression and >100-fold elevated cytokine secretion. The S.Tm TTSS-1 effectors SopB, SopE, and SopE2 here elicit a second activation signal, including Akt phosphorylation downstream of effector translocation, which combines with TLR activation to drive the full-blown mast cell response. Supernatants from S.Tm-infected mast cells boost macrophage survival and maturation from bone-marrow progenitors. Taken together, this study shows that mast cells can differentiate between extracellular and host-cell invasive enterobacteria via a two-step activation mechanism and tune their inflammatory output accordingly.", "doi": "10.1038/s41467-024-45057-w", "pmid": "38291037", "labels": {"Mikael Sellin": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC10828507"}, {"db": "pii", "key": "10.1038/s41467-024-45057-w"}], "notes": [], "created": "2024-11-25T16:25:09.599Z", "modified": "2024-11-25T16:25:09.822Z"}, {"entity": "publication", "iuid": "7a1f2bacf6804dfdaeadb202cb4f6f93", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/7a1f2bacf6804dfdaeadb202cb4f6f93.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/7a1f2bacf6804dfdaeadb202cb4f6f93"}}, "title": "High-efficiency transfection of<i>Acanthamoeba castellanii<\/i>using a cationic polymer", "authors": [{"family": "Moreno", "given": "Ana\u00edsa B", "initials": "AB", "orcid": "0000-0002-3229-4029", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/22821af48ff64059b3fa92e8acacd0c9.json"}}, {"family": "Ek", "given": "Viktor", "initials": "V", "orcid": "0000-0002-5039-8163", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a80b49fa9bd9407a8b806355e89ca201.json"}}, {"family": "Eriksson", "given": "Jens", "initials": "J", "orcid": "0000-0002-8945-2665", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe04815d524b48c2ba80c094c629362f.json"}}, {"family": "Sellin", "given": "Mikael E", "initials": "ME", "orcid": "0000-0002-8355-0803", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/559c18ec87d64318a0afc6267ea879e2.json"}}, {"family": "Guy", "given": "Lionel", "initials": "L", "orcid": "0000-0001-8354-2398", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/93e170c891c742838951a1fc8b50d223.json"}}], "type": "posted-content", "published": "2022-12-01", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2022.12.01.518696", "pmid": null, "labels": {"SciLifeLab Fellow": null, "Mikael Sellin": null}, "xrefs": [], "notes": [], "created": "2023-05-29T12:43:00.839Z", "modified": "2025-12-04T16:56:02.523Z"}, {"entity": "publication", "iuid": "19c5c3cd794b4250bb2a6ff65d9665f1", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/19c5c3cd794b4250bb2a6ff65d9665f1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/19c5c3cd794b4250bb2a6ff65d9665f1"}}, "title": "TGF\u03b2 selects for pro-stemness over pro-invasive phenotypes during cancer cell epithelial-mesenchymal transition.", "authors": [{"family": "Tsubakihara", "given": "Yutaro", "initials": "Y"}, {"family": "Ohata", "given": "Yae", "initials": "Y", "orcid": "0000-0002-5518-835X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/97ecb5ad5b6a4aa69a4d84523cb84918.json"}}, {"family": "Okita", "given": "Yukari", "initials": "Y", "orcid": "0000-0002-7279-4634", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/35f1dd6b5aa74ab9a53620c614680674.json"}}, {"family": "Younis", "given": "Shady", "initials": "S", "orcid": "0000-0002-4319-1738", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cd2c4773dcf84b9eb1b82d19e5e2039c.json"}}, {"family": "Eriksson", "given": "Jens", "initials": "J", "orcid": "0000-0002-8945-2665", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe04815d524b48c2ba80c094c629362f.json"}}, {"family": "Sellin", "given": "Mikael E", "initials": "ME", "orcid": "0000-0002-8355-0803", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/559c18ec87d64318a0afc6267ea879e2.json"}}, {"family": "Ren", "given": "Jiang", "initials": "J"}, {"family": "Ten Dijke", "given": "Peter", "initials": "P", "orcid": "0000-0002-7234-342X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2193ff2b5f924395ac6d4a9ddd53f20e.json"}}, {"family": "Miyazono", "given": "Kohei", "initials": "K", "orcid": "0000-0001-7341-0172", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/88b0a85433264e96a3c4f2e27ca0e3f7.json"}}, {"family": "Hikita", "given": "Atsuhiko", "initials": "A", "orcid": "0000-0001-9552-2976", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d8d3ea8a83164bb7af09a879dfe8c52f.json"}}, {"family": "Imamura", "given": "Takeshi", "initials": "T", "orcid": "0000-0001-5101-4304", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a694d49ba34d4aac8f6b73e21f0303e1.json"}}, {"family": "Kato", "given": "Mitsuyasu", "initials": "M", "orcid": "0000-0001-9905-2473", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/04d3edbf488a445583e31a14d7576aca.json"}}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH", "orcid": "0000-0002-9508-896X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5bca6678f5eb4baf853fca6ed5f9b726.json"}}, {"family": "Moustakas", "given": "Aristidis", "initials": "A", "orcid": "0000-0001-9131-3827", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f11771bffabf4da6a2a5e2668c7c7c2d.json"}}], "type": "journal article", "published": "2022-06-00", "journal": {"title": "Mol Oncol", "issn": "1878-0261", "volume": "16", "issue": "12", "pages": "2330-2354", "issn-l": "1574-7891"}, "abstract": "Transforming growth factor \u03b2 (TGF\u03b2) induces epithelial-mesenchymal transition (EMT), which correlates with stemness and invasiveness. Mesenchymal-epithelial transition (MET) is induced by TGF\u03b2 withdrawal and correlates with metastatic colonization. Whether TGF\u03b2 promotes stemness and invasiveness simultaneously via EMT remains unclear. We established a breast cancer cell model expressing red fluorescent protein (RFP) under the E-cadherin promoter. In 2D cultures, TGF\u03b2 induced EMT, generating RFPlow cells with a mesenchymal transcriptome, and regained RFP, with an epithelial transcriptome, after MET induced by TGF\u03b2 withdrawal. RFPlow cells generated robust mammospheres, with epithelio-mesenchymal cell surface features. Mammospheres that were forced to adhere generated migratory cells, devoid of RFP, a phenotype which was inhibited by a TGF\u03b2 receptor kinase inhibitor. Further stimulation of RFPlow mammospheres with TGF\u03b2 suppressed the generation of motile cells, but enhanced mammosphere growth. Accordingly, mammary fat-pad-transplanted mammospheres, in the absence of exogenous TGF\u03b2 treatment, established lung metastases with evident MET (RFPhigh cells). In contrast, TGF\u03b2-treated mammospheres revealed high tumour-initiating capacity, but limited metastatic potential. Thus, the biological context of partial EMT and MET allows TGF\u03b2 to differentiate between pro-stemness and pro-invasive phenotypes.", "doi": "10.1002/1878-0261.13215", "pmid": "35348275", "labels": {"SciLifeLab Fellow": null, "Mikael Sellin": null}, "xrefs": [{"db": "pmc", "key": "PMC9208077"}, {"db": "RefSeq", "key": "E-MTAB-97509"}], "notes": [], "created": "2022-12-04T11:00:00.977Z", "modified": "2022-12-04T11:00:01.263Z"}, {"entity": "publication", "iuid": "30796333893a4c4fb91ff06d1c2b2543", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/30796333893a4c4fb91ff06d1c2b2543.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/30796333893a4c4fb91ff06d1c2b2543"}}, "title": "A motile doublet form of Salmonella Typhimurium diversifies target search behavior at the epithelial surface.", "authors": [{"family": "Ek", "given": "Viktor", "initials": "V", "orcid": "0000-0002-5039-8163", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a80b49fa9bd9407a8b806355e89ca201.json"}}, {"family": "Fattinger", "given": "Stefan A", "initials": "SA", "orcid": "0000-0003-4899-4414", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2a3891756a0e46b7be8494556da9254f.json"}}, {"family": "Florbrant", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-1630-4442", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21b09621be1d4fe5a3c956360234b99d.json"}}, {"family": "Hardt", "given": "Wolf-Dietrich", "initials": "WD", "orcid": "0000-0002-9892-6420", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1049556a73b84d258e26a84382fe5870.json"}}, {"family": "Di Martino", "given": "Maria Letizia", "initials": "ML", "orcid": "0000-0002-9491-4000", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ccaa06e9e2d441589299b7e33ee55034.json"}}, {"family": "Eriksson", "given": "Jens", "initials": "J", "orcid": "0000-0002-8945-2665", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe04815d524b48c2ba80c094c629362f.json"}}, {"family": "Sellin", "given": "Mikael E", "initials": "ME", "orcid": "0000-0002-8355-0803", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/559c18ec87d64318a0afc6267ea879e2.json"}}], "type": "journal article", "published": "2022-05-00", "journal": {"title": "Mol. Microbiol.", "issn": "1365-2958", "volume": "117", "issue": "5", "pages": "1156-1172", "issn-l": "0950-382X"}, "abstract": "The behaviors of infectious bacteria are commonly studied in bulk. This is effective to define the general properties of a given isolate, but insufficient to resolve subpopulations and unique single-microbe behaviors within the bacterial pool. We here employ microscopy to study single-bacterium characteristics among Salmonella enterica serovar Typhimurium (S.Tm), as they prepare for and launch invasion of epithelial host cells. We find that during the bacterial growth cycle, S.Tm populations switch gradually from fast planktonic growth to a host cell-invasive phenotype, characterized by flagellar motility and expression of the Type-three-secretion-system-1. The indistinct nature of this shift leads to the establishment of a transient subpopulation of S.Tm \"doublets\"-waist-bearing bacteria anticipating cell division-which simultaneously express host cell invasion machinery. In epithelial cell culture infections, these S.Tm doublets outperform their \"singlet\" brethren and represent a hyperinvasive subpopulation. Atop both glass and enteroid-derived monolayers, doublets swim along markedly straighter trajectories than singlets, thereby diversifying search patterns and improving the surface exploration capacity of the total bacterial population. The straighter swimming, combined with an enhanced cell-adhesion propensity, suffices to account for the hyperinvasive doublet phenotype. This work highlights bacterial cell length heterogeneity as a key determinant of target search patterns atop epithelia.", "doi": "10.1111/mmi.14898", "pmid": "35332598", "labels": {"SciLifeLab Fellow": null, "Mikael Sellin": null}, "xrefs": [{"db": "pmc", "key": "PMC9325389"}], "notes": [], "created": "2022-12-04T10:59:59.629Z", "modified": "2022-12-04T10:59:59.686Z"}, {"entity": "publication", "iuid": "0e0f93d840f8415cb86e1c9dba0f1272", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0e0f93d840f8415cb86e1c9dba0f1272.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0e0f93d840f8415cb86e1c9dba0f1272"}}, "title": "High-Definition DIC Imaging Uncovers Transient Stages of Pathogen Infection Cycles on the Surface of Human Adult Stem Cell-Derived Intestinal Epithelium.", "authors": [{"family": "van Rijn", "given": "Jorik M", "initials": "JM", "orcid": "0000-0003-2865-4455", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/198177b1db8d4e8d867e86e3b3770aea.json"}}, {"family": "Eriksson", "given": "Jens", "initials": "J", "orcid": "0000-0002-8945-2665", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe04815d524b48c2ba80c094c629362f.json"}}, {"family": "Gr\u00fcttner", "given": "Jana", "initials": "J", "orcid": "0000-0002-2507-3375", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4a8bec9e9a2f4b5a92ae3a2aa6f57e7c.json"}}, {"family": "Sundbom", "given": "Magnus", "initials": "M", "orcid": "0000-0002-6243-2859", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dec44b4c4ce84ce6b04bf9506874246b.json"}}, {"family": "Webb", "given": "Dominic-Luc", "initials": "DL", "orcid": "0000-0002-6979-9194", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f8caab45e535418aa431bc55eca471e8.json"}}, {"family": "Hellstr\u00f6m", "given": "Per M", "initials": "PM", "orcid": "0000-0001-8428-0772", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f9627ff4daff4db2802135e0d06282e0.json"}}, {"family": "Sv\u00e4rd", "given": "Staffan G", "initials": "SG", "orcid": "0000-0002-7392-1746", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d3542be86984e928373e248f1c88b47.json"}}, {"family": "Sellin", "given": "Mikael E", "initials": "ME", "orcid": "0000-0002-8355-0803", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/559c18ec87d64318a0afc6267ea879e2.json"}}], "type": "journal article", "published": "2022-02-01", "journal": {"title": "MBio", "issn": "2150-7511", "volume": "13", "issue": "1", "pages": "e0002222", "issn-l": null}, "abstract": "Interactions between individual pathogenic microbes and host tissues involve fast and dynamic processes that ultimately impact the outcome of infection. Using live-cell microscopy, these dynamics can be visualized to study, e.g., microbe motility, binding and invasion of host cells, and intrahost-cell survival. Such methodology typically employs confocal imaging of fluorescent tags in tumor-derived cell line infections on glass. This allows high-definition imaging but poorly reflects the host tissue's physiological architecture and may result in artifacts. We developed a method for live-cell imaging of microbial infection dynamics on human adult stem cell-derived intestinal epithelial cell (IEC) layers. These IEC layers are grown in apical imaging chambers, optimized for physiological cell arrangement and fast, but gentle, differential interference contrast (DIC) imaging. This allows subsecond visualization of both microbial and epithelial surface ultrastructure at high resolution without using fluorescent reporters. We employed this technology to probe the behavior of two model pathogens, Salmonella enterica serovar Typhimurium and Giardia intestinalis, at the intestinal epithelial surface. Our results reveal pathogen-specific swimming patterns on the epithelium and show that Salmonella lingers on the IEC surface for prolonged periods before host cell invasion, while Giardia uses circular swimming with intermittent attachments to scout for stable adhesion sites. The method even permits tracking of individual Giardia flagella, demonstrating that active flagellar beating and attachment to the IEC surface are not mutually exclusive. This work describes a generalizable and relatively inexpensive approach to resolving dynamic pathogen-IEC layer interactions, applicable even to genetically nontractable microorganisms. IMPORTANCE Knowledge of dynamic niche-specific interactions between single microbes and host cells is essential to understand infectious disease progression. However, advances in this field have been hampered by the inherent conflict between the technical requirements for high-resolution live-cell imaging on the one hand and conditions that best mimic physiological infection niche parameters on the other. Toward bridging this divide, we present a methodology for differential interference contrast (DIC) imaging of pathogen interactions at the apical surface of enteroid-derived intestinal epithelia, providing both high spatial and temporal resolution. This alleviates the need for fluorescent reporters in live-cell imaging and provides dynamic information about microbe interactions with a nontransformed, confluent, polarized, and microvilliated human gut epithelium. Using this methodology, we uncover previously unrecognized stages of Salmonella and Giardia infection cycles at the epithelial surface.", "doi": "10.1128/mbio.00022-22", "pmid": "35100876", "labels": {"SciLifeLab Fellow": null, "Mikael Sellin": null}, "xrefs": [{"db": "pmc", "key": "PMC8805028"}], "notes": [], "created": "2022-12-04T10:59:58.141Z", "modified": "2022-12-04T10:59:58.288Z"}, {"entity": "publication", "iuid": "c1f8cf6dd77e4c37bf3981a01d459948", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c1f8cf6dd77e4c37bf3981a01d459948.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c1f8cf6dd77e4c37bf3981a01d459948"}}, "title": "Bacterial detection by NAIP/NLRC4 elicits prompt contractions of intestinal epithelial cell layers.", "authors": [{"family": "Samperio Ventayol", "given": "Pilar", "initials": "P", "orcid": "0000-0002-3726-7871", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e7647686922142a8b8bd8629142445fc.json"}}, {"family": "Geiser", "given": "Petra", "initials": "P", "orcid": "0000-0003-2785-4201", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0487e44d013c4faea6523a9f4b23cbe6.json"}}, {"family": "Di Martino", "given": "Maria Letizia", "initials": "ML", "orcid": "0000-0002-9491-4000", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ccaa06e9e2d441589299b7e33ee55034.json"}}, {"family": "Florbrant", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-1630-4442", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21b09621be1d4fe5a3c956360234b99d.json"}}, {"family": "Fattinger", "given": "Stefan A", "initials": "SA", "orcid": "0000-0003-4899-4414", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2a3891756a0e46b7be8494556da9254f.json"}}, {"family": "Walder", "given": "Naemi", "initials": "N", "orcid": "0000-0002-2155-8527", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3f7de8ba54dc49568357b6f5c69681a5.json"}}, {"family": "Sima", "given": "Eduardo", "initials": "E", "orcid": "0000-0001-7373-4767", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a9855115aad340e3a1b9ecf05afb3b9d.json"}}, {"family": "Shao", "given": "Feng", "initials": "F", "orcid": "0000-0002-9562-7791", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e64e1601b52746f5b81e2331a9bc58ab.json"}}, {"family": "Gekara", "given": "Nelson O", "initials": "NO", "orcid": "0000-0002-1269-8288", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/50781c8782ed4c78a8c993a97bef9661.json"}}, {"family": "Sundbom", "given": "Magnus", "initials": "M", "orcid": "0000-0002-6243-2859", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dec44b4c4ce84ce6b04bf9506874246b.json"}}, {"family": "Hardt", "given": "Wolf-Dietrich", "initials": "WD", "orcid": "0000-0002-9892-6420", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1049556a73b84d258e26a84382fe5870.json"}}, {"family": "Webb", "given": "Dominic-Luc", "initials": "DL", "orcid": "0000-0002-6979-9194", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f8caab45e535418aa431bc55eca471e8.json"}}, {"family": "Hellstr\u00f6m", "given": "Per M", "initials": "PM", "orcid": "0000-0001-8428-0772", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f9627ff4daff4db2802135e0d06282e0.json"}}, {"family": "Eriksson", "given": "Jens", "initials": "J", "orcid": "0000-0002-8945-2665", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe04815d524b48c2ba80c094c629362f.json"}}, {"family": "Sellin", "given": "Mikael E", "initials": "ME", "orcid": "0000-0002-8355-0803", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/559c18ec87d64318a0afc6267ea879e2.json"}}], "type": "journal article", "published": "2021-04-20", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "118", "issue": "16", "issn-l": "0027-8424"}, "abstract": "The gut epithelium serves to maximize the surface for nutrient and fluid uptake, but at the same time must provide a tight barrier to pathogens and remove damaged intestinal epithelial cells (IECs) without jeopardizing barrier integrity. How the epithelium coordinates these tasks remains a question of significant interest. We used imaging and an optical flow analysis pipeline to study the dynamicity of untransformed murine and human intestinal epithelia, cultured atop flexible hydrogel supports. Infection with the pathogen Salmonella Typhimurium (STm) within minutes elicited focal contractions with inward movements of up to \u223c1,000 IECs. Genetics approaches and chimeric epithelial monolayers revealed contractions to be triggered by the NAIP/NLRC4 inflammasome, which sensed type-III secretion system and flagellar ligands upon bacterial invasion, converting the local tissue into a contraction epicenter. Execution of the response required swift sublytic Gasdermin D pore formation, ion fluxes, and the propagation of a myosin contraction pulse across the tissue. Importantly, focal contractions preceded, and could be uncoupled from, the death and expulsion of infected IECs. In both two-dimensional monolayers and three-dimensional enteroids, multiple infection-elicited contractions coalesced to produce shrinkage of the epithelium as a whole. Monolayers deficient for Caspase-1(-11) or Gasdermin D failed to elicit focal contractions but were still capable of infected IEC death and expulsion. Strikingly, these monolayers lost their integrity to a markedly higher extent than wild-type counterparts. We propose that prompt NAIP/NLRC4/Caspase-1/Gasdermin D/myosin-dependent contractions allow the epithelium to densify its cell packing in infected regions, thereby preventing tissue disintegration due to the subsequent IEC death and expulsion process.", "doi": "10.1073/pnas.2013963118", "pmid": "33846244", "labels": {"Mikael Sellin": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "2013963118"}, {"db": "pmc", "key": "PMC8072224"}], "notes": [], "created": "2021-12-05T09:46:51.321Z", "modified": "2022-11-04T11:32:13.392Z"}, {"entity": "publication", "iuid": "86df9ee756b14980a3d708696efa2aca", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/86df9ee756b14980a3d708696efa2aca.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/86df9ee756b14980a3d708696efa2aca"}}, "title": "Cellocity: A Python package for analysis of confluent cell layer dynamics", "authors": [{"family": "Eriksson", "given": "Jens", "initials": "J", "orcid": "0000-0002-8945-2665", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe04815d524b48c2ba80c094c629362f.json"}}, {"family": "Styrstr\u00f6m", "given": "Daniel", "initials": "D"}, {"family": "Sellin", "given": "Mikael", "initials": "M", "orcid": "0000-0002-8355-0803", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/559c18ec87d64318a0afc6267ea879e2.json"}}], "type": "journal-article", "published": "2021-01-28", "journal": {"title": "JOSS", "issn": "2475-9066", "volume": "6", "issue": "57", "pages": "2818", "issn-l": null}, "abstract": null, "doi": "10.21105/joss.02818", "pmid": null, "labels": {"Mikael Sellin": null, "SciLifeLab Fellow": null}, "xrefs": [], "notes": [], "created": "2021-12-05T09:49:15.314Z", "modified": "2025-12-04T17:06:59.541Z"}, {"entity": "publication", "iuid": "a088c580747242cc9cfc7c25f2b79601", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a088c580747242cc9cfc7c25f2b79601.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a088c580747242cc9cfc7c25f2b79601"}}, "title": "Salmonella enterica Serovar Typhimurium Exploits Cycling through Epithelial Cells To Colonize Human and Murine Enteroids.", "authors": [{"family": "Geiser", "given": "Petra", "initials": "P", "orcid": "0000-0003-2785-4201", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0487e44d013c4faea6523a9f4b23cbe6.json"}}, {"family": "Di Martino", "given": "Maria Letizia", "initials": "ML", "orcid": "0000-0002-9491-4000", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ccaa06e9e2d441589299b7e33ee55034.json"}}, {"family": "Samperio Ventayol", "given": "Pilar", "initials": "P", "orcid": "0000-0002-3726-7871", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e7647686922142a8b8bd8629142445fc.json"}}, {"family": "Eriksson", "given": "Jens", "initials": "J", "orcid": "0000-0002-8945-2665", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fe04815d524b48c2ba80c094c629362f.json"}}, {"family": "Sima", "given": "Eduardo", "initials": "E", "orcid": "0000-0001-7373-4767", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a9855115aad340e3a1b9ecf05afb3b9d.json"}}, {"family": "Al-Saffar", "given": "Anas Kh", "initials": "AK", "orcid": "0000-0002-4842-3227", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6fbadd286ab040e0a6f1a045b60aa52a.json"}}, {"family": "Ahl", "given": "David", "initials": "D", "orcid": "0000-0003-4364-8571", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/17570499e2b64bd697c4beaf9c679c07.json"}}, {"family": "Phillipson", "given": "Mia", "initials": "M", "orcid": "0000-0002-2387-0266", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/265c9b3e11de4fcaa270a0eb20faf65c.json"}}, {"family": "Webb", "given": "Dominic-Luc", "initials": "DL", "orcid": "0000-0002-6979-9194", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f8caab45e535418aa431bc55eca471e8.json"}}, {"family": "Sundbom", "given": "Magnus", "initials": "M", "orcid": "0000-0002-6243-2859", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dec44b4c4ce84ce6b04bf9506874246b.json"}}, {"family": "Hellstr\u00f6m", "given": "Per M", "initials": "PM", "orcid": "0000-0001-8428-0772", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f9627ff4daff4db2802135e0d06282e0.json"}}, {"family": "Sellin", "given": "Mikael E", "initials": "ME", "orcid": "0000-0002-8355-0803", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/559c18ec87d64318a0afc6267ea879e2.json"}}], "type": "journal article", "published": "2021-01-12", "journal": {"title": "MBio", "issn": "2150-7511", "volume": "12", "issue": "1", "issn-l": null}, "abstract": "Enterobacterial pathogens infect the gut by a multistep process, resulting in colonization of both the lumen and the mucosal epithelium. Due to experimental constraints, it remains challenging to address how luminal and epithelium-lodged pathogen populations cross-feed each other in vivo Enteroids are cultured three-dimensional miniature intestinal organs with a single layer of primary intestinal epithelial cells (IECs) surrounding a central lumen. They offer new opportunities to study enterobacterial infection under near-physiological conditions, at a temporal and spatial resolution not attainable in animal models, but remain poorly explored in this context. We employed microinjection, time-lapse microscopy, bacterial genetics, and barcoded consortium infections to describe the complete infection cycle of Salmonella enterica serovar Typhimurium in both human and murine enteroids. Flagellar motility and type III secretion system 1 (TTSS-1) promoted Salmonella Typhimurium targeting of the intraepithelial compartment and breaching of the epithelial barrier. Strikingly, however, TTSS-1 also potently boosted colonization of the enteroid lumen. By tracing the infection over time, we identified a cycle(s) of TTSS-1-driven IEC invasion, intraepithelial replication, and reemergence through infected IEC expulsion as a key mechanism for Salmonella Typhimurium luminal colonization. These findings suggest a positive feed-forward loop, through which IEC invasion by planktonic bacteria fuels further luminal population expansion, thereby ensuring efficient colonization of both the intraepithelial and luminal niches.IMPORTANCE Pathogenic gut bacteria are common causes of intestinal disease. Enteroids-cultured three-dimensional replicas of the mammalian gut-offer an emerging model system to study disease mechanisms under conditions that recapitulate key features of the intestinal tract. In this study, we describe the full life cycle of the prototype gut pathogen Salmonella enterica serovar Typhimurium within human and mouse enteroids. We map the consecutive steps and define the bacterial virulence factors that drive colonization of luminal and epithelial compartments, as well as breaching of the epithelial barrier. Strikingly, our work reveals how bacterial colonization of the epithelium potently fuels expansion also in the luminal compartment, through a mechanism involving the death and expulsion of bacterium-infected epithelial cells. These findings have repercussions for our understanding of the Salmonella infection cycle. Moreover, our work provides a comprehensive foundation for the use of microinjected enteroids to model gut bacterial diseases.", "doi": "10.1128/mBio.02684-20", "pmid": "33436434", "labels": {"Mikael Sellin": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "mBio.02684-20"}, {"db": "pmc", "key": "PMC7844539"}], "notes": [], "created": "2021-12-05T09:46:54.328Z", "modified": "2022-11-04T11:32:13.749Z"}]}