{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T21:00:06Z","timestamp":1765486806528,"version":"3.41.2"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AI124260, U01AI160421"],"award-info":[{"award-number":["U01AI124260, U01AI160421"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p><jats:italic>Ov<\/jats:italic>-<jats:italic>ASP-1<\/jats:italic> (rASP-1), a parasite-derived protein secreted by the helminth <jats:italic>Onchocerca volvulus<\/jats:italic>, is an adjuvant which enhances the potency of the influenza trivalent vaccine (IIV3), even when used with 40-fold less IIV3. This study is aimed to provide a deeper insight into the molecular networks that underline the adjuvanticity of rASP-1. Here we show that rASP-1 stimulates mouse CD11c<jats:sup>+<\/jats:sup> bone marrow-derived dendritic (BMDCs) to secrete elevated levels of IL-12p40, TNF-\u03b1, IP-10 and IFN-\u03b2 in a TRIF-dependent but MyD88-independent manner. rASP-1-activated BMDCs promoted the differentiation of na\u00efve CD4<jats:sup>+<\/jats:sup> T cells into Th1 cells (IFN-\u03b3<jats:sup>+<\/jats:sup>) that was TRIF- and type I interferon receptor (IFNAR)-dependent, and into Tfh-like cells (IL21<jats:sup>+<\/jats:sup>) and Tfh1 (IFN-\u03b3<jats:sup>+<\/jats:sup> IL21<jats:sup>+)<\/jats:sup> that were TRIF-, MyD88- and IFNAR-dependent. rASP-1-activated BMDCs promoted the differentiation of na\u00efve CD4<jats:sup>+<\/jats:sup> T cells into Th17 (IL-17<jats:sup>+<\/jats:sup>) cells only when the MyD88 pathway was inhibited. Importantly, rASP-1-activated human blood cDCs expressed upregulated genes that are associated with DC maturation, type I IFN and type II IFN signaling, as well as TLR4-TRIF dependent signaling. These activated cDCs promoted the differentiation of na\u00efve human CD4<jats:sup>+<\/jats:sup> T cells into Th1, Tfh-like and Th17 cells. Our data thus confirms that the rASP-1 is a potent innate adjuvant that polarizes the adaptive T cell responses to Th1\/Tfh1 in both mouse and human DCs. Notably, the rASP-1-adjuvanted IIV3 vaccine elicited protection of mice from a lethal H1N1 infection that is also dependent on the TLR4-TRIF axis and IFNAR signaling pathway, as well as on its ability to induce anti-IIV3 antibody production.<\/jats:p>","DOI":"10.3389\/fimmu.2022.961094","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T05:35:03Z","timestamp":1662096903000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The Th1\/Tfh-like biased responses elicited by the rASP-1 innate adjuvant are dependent on TRIF and Type I IFN receptor pathways"],"prefix":"10.3389","volume":"13","author":[{"given":"Parakkal Jovvian","family":"George","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radu","family":"Marches","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Djamel","family":"Nehar-Belaid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Banchereau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Lustigman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/s41577-020-00479-7","article-title":"A guide to vaccinology: from basic principles to new developments","volume":"21","author":"Pollard","year":"2021","journal-title":"Nat Rev 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