{"entity": "researcher", "timestamp": "2026-07-20T23:09:23.667Z", "family": "Hellstr\u00f6m", "given": "Per M", "initials": "PM", "orcid": "0000-0001-8428-0772", "affiliations": ["Department of Medical Sciences, Gastroenterology and Hepatology Unit, Uppsala University, 75185 Uppsala, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/f9627ff4daff4db2802135e0d06282e0.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/f9627ff4daff4db2802135e0d06282e0"}}, "publications": [{"entity": "publication", "iuid": "c2edd04be55b41629836b51cdcbb1849", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c2edd04be55b41629836b51cdcbb1849.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c2edd04be55b41629836b51cdcbb1849"}}, "title": "Trophozoite fitness dictates the intestinal epithelial cell response to Giardia intestinalis infection.", "authors": [{"family": "Gr\u00fcttner", "given": "Jana", "initials": "J", "orcid": "0000-0002-2507-3375", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4a8bec9e9a2f4b5a92ae3a2aa6f57e7c.json"}}, {"family": "van Rijn", "given": "Jorik M", "initials": "JM", "orcid": "0000-0003-2865-4455", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/198177b1db8d4e8d867e86e3b3770aea.json"}}, {"family": "Geiser", "given": "Petra", "initials": "P", "orcid": "0000-0003-2785-4201", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0487e44d013c4faea6523a9f4b23cbe6.json"}}, {"family": "Florbrant", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-1630-4442", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/21b09621be1d4fe5a3c956360234b99d.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": "Sundbom", "given": "Magnus", "initials": "M", "orcid": "0000-0002-6243-2859", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dec44b4c4ce84ce6b04bf9506874246b.json"}}, {"family": "Sellin", "given": "Mikael E", "initials": "ME", "orcid": "0000-0002-8355-0803", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/559c18ec87d64318a0afc6267ea879e2.json"}}, {"family": "Sv\u00e4rd", "given": "Staffan G", "initials": "SG", "orcid": "0000-0002-7392-1746", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d3542be86984e928373e248f1c88b47.json"}}], "type": "journal article", "published": "2023-05-00", "journal": {"title": "PLoS Pathog", "issn": "1553-7374", "volume": "19", "issue": "5", "pages": "e1011372", "issn-l": "1553-7366"}, "abstract": "Giardia intestinalis is a non-invasive, protozoan parasite infecting the upper small intestine of most mammals. Symptomatic infections cause the diarrhoeal disease giardiasis in humans and animals, but at least half of the infections are asymptomatic. However, the molecular underpinnings of these different outcomes of the infection are still poorly defined. Here, we studied the early transcriptional response to G. intestinalis trophozoites, the disease-causing life-cycle stage, in human enteroid-derived, 2-dimensional intestinal epithelial cell (IEC) monolayers. Trophozoites preconditioned in media that maximise parasite fitness triggered only neglectable inflammatory transcription in the IECs during the first hours of co-incubation. By sharp contrast, \"non-fit\" or lysed trophozoites induced a vigorous IEC transcriptional response, including high up-regulation of many inflammatory cytokines and chemokines. Furthermore, \"fit\" trophozoites could even suppress the stimulatory effect of lysed trophozoites in mixed infections, suggesting active G. intestinalis suppression of the IEC response. By dual-species RNA-sequencing, we defined the IEC and G. intestinalis gene expression programs associated with these differential outcomes of the infection. Taken together, our results inform on how G. intestinalis infection can lead to such highly variable effects on the host, and pinpoints trophozoite fitness as a key determinant of the IEC response to this common parasite.", "doi": "10.1371/journal.ppat.1011372", "pmid": "37141303", "labels": {"SciLifeLab Fellow": null, "Mikael Sellin": null}, "xrefs": [{"db": "pmc", "key": "PMC10187934"}, {"db": "pii", "key": "PPATHOGENS-D-22-02213"}], "notes": [], "created": "2023-12-01T13:09:43.844Z", "modified": "2023-12-01T13:09:43.926Z"}, {"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": "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"}]}