{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T10:03:23Z","timestamp":1785578603585,"version":"3.56.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Canine<jats:italic>Leptospira<\/jats:italic>vaccines contain inactivated strains of pathogenic<jats:italic>Leptospira<\/jats:italic>, the causative agents of leptospirosis. For an effective response to vaccination, activation of the innate immune system<jats:italic>via<\/jats:italic>pattern recognition receptors such as TLRs is crucial. However, it is not known which TLRs are activated by<jats:italic>Leptospira<\/jats:italic>in dogs. To investigate the involvement of canine TLR2, TLR4, and TLR5 in the recognition of<jats:italic>Leptospira<\/jats:italic>, we stimulated canine moDC and reporter cells expressing canine TLR2 with either whole-inactivated bacteria or purified LPS of<jats:italic>Leptospira<\/jats:italic>strains, representing the serogroups generally used in canine leptospirosis vaccines. Using the endotoxin neutralizing reagent polymyxin B and TLR4 antagonist RS-LPS, we demonstrate that<jats:italic>Leptospira<\/jats:italic>LPS and canine TLR4 are involved in IL-1\u03b2 production as well as in the uptake of inactivated<jats:italic>Leptospira<\/jats:italic>in canine moDC. Furthermore, polymyxin B only partially inhibited IL-1\u03b2 production induced by inactivated<jats:italic>Leptospira<\/jats:italic>, suggesting that next to TLR4, also other TLRs may be involved. The observed activation of canine TLR2-expressing reporter cells by inactivated<jats:italic>Leptospira<\/jats:italic>strains indicates that TLR2 could be one of these TLRs. Next, we analyzed TLR2 and TLR4 activating capabilities by the same<jats:italic>Leptospira<\/jats:italic>strains using human and mouse TLR-expressing reporter cells. Inactivated<jats:italic>Leptospira<\/jats:italic>and leptospiral LPS activated not only mouse, but also human TLR4 and this activation was shown to be LPS dependent in both cases. Additionally, inactivated<jats:italic>Leptospira<\/jats:italic>activated mouse and human TLR2-expressing reporter cell lines. In our study, we could not identify significant species differences in the recognition of<jats:italic>Leptospira<\/jats:italic>by TLR2 and TLR4 between dog, human and mouse. Lastly, we show that these inactivated<jats:italic>Leptospira<\/jats:italic>strains are recognized by both mouse and human TLR5 reporter cells only after exposure to additional heat-treatment. Unfortunately, we were not able to confirm this in the canine system. Our data show that TLR2 and TLR4 are involved in the recognition of<jats:italic>Leptospira<\/jats:italic>strains used in the production of canine<jats:italic>Leptospira<\/jats:italic>vaccines. This study contributes to the understanding of<jats:italic>Leptospira<\/jats:italic>-induced innate immune responses in dogs, humans, and mice. Future studies are needed to further explore the role of canine TLR2, TLR4 and TLR5 in the induction of vaccine-mediated immunity against<jats:italic>Leptospira<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fimmu.2022.823058","type":"journal-article","created":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T01:22:44Z","timestamp":1648084964000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Activation of Canine, Mouse and Human TLR2 and TLR4 by Inactivated Leptospira Vaccine Strains"],"prefix":"10.3389","volume":"13","author":[{"given":"Andreja","family":"Novak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elder","family":"Pupo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"van\u2019t Veld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor P. 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