{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:53:33Z","timestamp":1790607213199,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009970","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:00:00Z","timestamp":1634083200000}}],"reference-count":85,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"national institute of allergy and infectious diseases","doi-asserted-by":"publisher","award":["AI139628"],"award-info":[{"award-number":["AI139628"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"national institute of general medical sciences","doi-asserted-by":"publisher","award":["P30 GM110907"],"award-info":[{"award-number":["P30 GM110907"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Toxoplasma gondii<\/jats:italic>is an orally acquired pathogen that induces strong IFN-\u03b3 based immunity conferring protection but that can also be the cause of immunopathology. The response in mice is driven in part by well-characterized MyD88-dependent signaling pathways. Here we focus on induction of less well understood immune responses that do not involve this Toll-like receptor (TLR)\/IL-1 family receptor adaptor molecule, in particular as they occur in the intestinal mucosa. Using eYFP-IL-12p40 reporter mice on an<jats:italic>MyD88<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup>background, we identified dendritic cells, macrophages, and neutrophils as cellular sources of MyD88-independent IL-12 after peroral<jats:italic>T<\/jats:italic>.<jats:italic>gondii<\/jats:italic>infection. Infection-induced IL-12 was lower in the absence of MyD88, but was still clearly above noninfected levels. Overall, this carried through to the IFN-\u03b3 response, which while generally decreased was still remarkably robust in the absence of MyD88. In the latter mice, IL-12 was strictly required to induce type I immunity. Type 1 and type 3 innate lymphoid cells (ILC), CD4<jats:sup>+<\/jats:sup>T cells, and CD8<jats:sup>+<\/jats:sup>T cells each contributed to the IFN-\u03b3 pool. We report that ILC3 were expanded in infected<jats:italic>MyD88<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup>mice relative to their<jats:italic>MyD88<\/jats:italic><jats:sup>+\/+<\/jats:sup>counterparts, suggesting a compensatory response triggered by loss of MyD88. Furthermore, bacterial flagellin and<jats:italic>Toxoplasma<\/jats:italic>specific CD4<jats:sup>+<\/jats:sup>T cell populations in the lamina propria expanded in response to infection in both WT and KO mice. Finally, we show that My88-independent IL-12 and T cell mediated IFN-\u03b3 production require the presence of the intestinal microbiota. Our results identify MyD88-independent intestinal immune pathways induced by<jats:italic>T<\/jats:italic>.<jats:italic>gondii<\/jats:italic>including myeloid cell derived IL-12 production, downstream type I immunity and IFN-\u03b3 production by ILC1, ILC3, and T lymphocytes. Collectively, our data reveal an underlying network of immune responses that do not involve signaling through MyD88.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009970","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T19:32:58Z","timestamp":1633116778000},"page":"e1009970","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Induction of IL-12p40 and type 1 immunity by Toxoplasma gondii in the absence of the TLR-MyD88 signaling cascade"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9017-0155","authenticated-orcid":true,"given":"Lindsay M.","family":"Snyder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2583-3258","authenticated-orcid":true,"given":"Claire M.","family":"Doherty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather L.","family":"Mercer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9020-3327","authenticated-orcid":true,"given":"Eric Y.","family":"Denkers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"key":"ppat.1009970.ref001","unstructured":"Parasites- Toxoplasmosis Centers for Disease Control and Prevention2018 [March 23, 2020]. https:\/\/www.cdc.gov\/parasites\/toxoplasmosis\/index.html."},{"key":"ppat.1009970.ref002","first-page":"1","volume-title":"Toxoplasma gondii The model apicomplexan: Perspective and methods","author":"JP Dubey","year":"2013","edition":"2"},{"key":"ppat.1009970.ref003","first-page":"100","volume-title":"Toxoplasma gondii The 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