{"entity": "researcher", "timestamp": "2026-10-05T21:32:28.361Z", "family": "Prensa", "given": "Grisna I", "initials": "GI", "orcid": "0009-0002-7101-7224", "affiliations": ["Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/3d030d78925948d993999b66e1959acc.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/3d030d78925948d993999b66e1959acc"}}, "publications": [{"entity": "publication", "iuid": "f94b305344964e2abd50b277f36990ad", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f94b305344964e2abd50b277f36990ad.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f94b305344964e2abd50b277f36990ad"}}, "title": "Mast Cell Phenotypic Heterogeneity Impacts the Interplay with Pathogenic Salmonella Typhimurium Bacteria.", "authors": [{"family": "von Beek", "given": "Christopher", "initials": "C", "orcid": "0000-0001-6310-7583", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3ea7730832f4f45ae6583076d90418a.json"}}, {"family": "Prensa", "given": "Grisna I", "initials": "GI", "orcid": "0009-0002-7101-7224", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d030d78925948d993999b66e1959acc.json"}}, {"family": "Andersson", "given": "Julia H M", "initials": "JHM"}, {"family": "Pejler", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-6779-391X", "researcher": {"href": "https://publications.scilifelab.se/researcher/97b2d5f8dec04bc3b7631370d77a2236.json"}}, {"family": "Sellin", "given": "Mikael E", "initials": "ME", "orcid": "0000-0002-8355-0803", "researcher": {"href": "https://publications.scilifelab.se/researcher/f797357bcd3d4447bff96c20873dd500.json"}}], "type": "journal article", "published": "2025-08-00", "journal": {"title": "Eur. J. Immunol.", "issn": "1521-4141", "volume": "55", "issue": "8", "pages": "e70040", "issn-l": "0014-2980"}, "abstract": "Mast cells (MCs) lodge within barrier tissues and respond to infectious microbes. Recent work demonstrated that MCs differentiate their cytokine response to extracellular versus invasive Gram-negative enterobacteria by a two-step activation mechanism that integrates Toll-like-receptor (TLR) sensing with signals elicited by type-III-secretion-system (TTSS) effectors during bacterial invasion. However, multiple MC subtypes exist, and it remains unclear how their phenotypic heterogeneity impacts microbial interactions. We find that murine MCs maintained in IL-3, or differentiated toward a connective-tissue phenotype (CT-MCs), respond potently to the enteropathogen Salmonella enterica Typhimurium (S.Tm) through two-step activation, with the TLR component explained by functional TLR4 and TLR2. By contrast, murine mucosal mast cells (M-MCs) express insignificant levels of these TLRs, therefore being unresponsive to extracellular S.Tm, but still mounting a response to invasive bacteria. Following invasion, MC granule maintenance by serglycin restricts S.Tm vacuolar and cytosolic colonization. Notably, this has no impact on the cytokine release from infected MCs, thus uncoupling S.Tm\u00b4s intracellular life-cycle from the MC cytokine response. Finally, human LUVA MCs employ a variant of two-step activation where TLR2/6 signaling combines with the TTSS-elicited signals. Together, this study explains how MC subtypes can respond differently to S.Tm-infection depending on their TLR expression and granule features.", "doi": "10.1002/eji.70040", "pmid": "40838737", "labels": {"NGI Short read": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12369454"}], "notes": [], "created": "2025-09-08T07:06:53.513Z", "modified": "2025-09-09T13:13:50.740Z"}, {"entity": "publication", "iuid": "bd2469b856a34c23bf93587d768559f2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bd2469b856a34c23bf93587d768559f2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bd2469b856a34c23bf93587d768559f2"}}, "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.scilifelab.se/researcher/a3ea7730832f4f45ae6583076d90418a.json"}}, {"family": "Fahlgren", "given": "Anna", "initials": "A"}, {"family": "Geiser", "given": "Petra", "initials": "P", "orcid": "0000-0003-2785-4201", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae0bf10f41dc4698b19288809bae2dd6.json"}}, {"family": "Di Martino", "given": "Maria Letizia", "initials": "ML", "orcid": "0000-0002-9491-4000", "researcher": {"href": "https://publications.scilifelab.se/researcher/708eae058cb3494f8407574a666a16f0.json"}}, {"family": "Lindahl", "given": "Otto", "initials": "O", "orcid": "0000-0001-7518-9483", "researcher": {"href": "https://publications.scilifelab.se/researcher/78053dd357c3435ba53aff83f06f28a4.json"}}, {"family": "Prensa", "given": "Grisna I", "initials": "GI", "orcid": "0009-0002-7101-7224", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d030d78925948d993999b66e1959acc.json"}}, {"family": "Mendez-Enriquez", "given": "Erika", "initials": "E", "orcid": "0000-0002-2114-2812", "researcher": {"href": "https://publications.scilifelab.se/researcher/dae73474be904a638ec13a8f704a9154.json"}}, {"family": "Eriksson", "given": "Jens", "initials": "J", "orcid": "0000-0002-8945-2665", "researcher": {"href": "https://publications.scilifelab.se/researcher/b94e7f542841474d86d53aa48958f870.json"}}, {"family": "Hallgren", "given": "Jenny", "initials": "J", "orcid": "0000-0002-3685-5364", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe8b929dbe60446f96db17a5eb2ba6f3.json"}}, {"family": "F\u00e4llman", "given": "Maria", "initials": "M", "orcid": "0000-0001-6874-6384", "researcher": {"href": "https://publications.scilifelab.se/researcher/cadcd4e3e63742e7b9cbbb74907bf9fc.json"}}, {"family": "Pejler", "given": "Gunnar", "initials": "G"}, {"family": "Sellin", "given": "Mikael E", "initials": "ME", "orcid": "0000-0002-8355-0803", "researcher": {"href": "https://publications.scilifelab.se/researcher/f797357bcd3d4447bff96c20873dd500.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": {"NGI Short read": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10828507"}, {"db": "pii", "key": "10.1038/s41467-024-45057-w"}], "notes": [], "created": "2024-03-21T12:10:55.423Z", "modified": "2024-03-21T12:10:55.804Z"}]}