{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:59:40Z","timestamp":1793332780711,"version":"4.5.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Resistance or susceptibility to\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    infection is dependent on the host immunological profile. Innate immune receptors, such as Toll-like receptors (TLRs\/TLR2, TLR4, TLR7, and TLR9) and Nod-like receptors (NLRs\/NOD1 and NLRP3 inflammasome) are involved with the resistance against acute experimental\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    infection. Here, we evaluated the impact of\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    virulence on the expression of innate immune receptors and its products in mice. For that, we used six\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    strains\/isolates that showed low (AM64\/TcIV and 3253\/Tc-V), medium (PL1.10.14\/TcIII and CL\/TcVI), or high (Colombian\/Tc-I and Y\/TcII) virulence and pathogenicity to the vertebrate host and belonging to the six discrete typing units (DTUs)\u2014TcI to TcVI. Parasitemia, mortality, and myocarditis were evaluated and correlated to the expression of TLRs, NLRs, adapter molecules, cytokines, and iNOS in myocardium by real time PCR. Cytokines (IL-1\u03b2, IL-12, TNF-\u03b1, and IFN-\n                    <jats:italic>\u03b3<\/jats:italic>\n                    ) were quantified in sera 15 days after infection. Our data indicate that high virulent strains of\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    , which generate high parasitemia, severe myocarditis, and 100% mortality in infected mice, inhibit the expression of TLR2, TLR4, TLR9, TRIF, and Myd88 transcripts, leading to a low IL-12 production, when compared to medium and low virulent\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    strains. On the other hand, the high virulent\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    strains induce the upregulation of NLRP3, caspase-1, IL-1\u03b2, TNF-\u03b1, and iNOS mRNA in heart muscle, compared to low and medium virulent strains, which may contribute to myocarditis and death. Moreover, high virulent strains induce higher levels of IL-1\u03b2 and TNF-\u03b1 in sera compared to less virulent parasites. Altogether the data indicate that differential TLR and NLR expression in heart muscle is correlated with virulence and pathogenicity of\n                    <jats:italic>T cruzi<\/jats:italic>\n                    strains. A better knowledge of the immunological mechanisms involved in resistance to\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    infection is important to understand the natural history of Chagas disease, can lead to identification of immunological markers and\/or to serve as a basis for alternative therapies.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2021.696719","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T07:01:35Z","timestamp":1626332495000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":31,"title":["Virulence of Trypanosoma cruzi Strains Is Related to the Differential Expression of Innate Immune Receptors in the Heart"],"prefix":"10.3389","volume":"11","author":[{"given":"Tamyres Bernadete Dantas","family":"Queiroga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie de Sena","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis Dantas da","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9ber de Mesquita","family":"Andrade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimundo Fernandes de","family":"Ara\u00fajo J\u00fanior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Ramon do Nascimento","family":"Brito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00facia Maria da Cunha","family":"Galv\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f4nia Cl\u00e1udia J\u00e1come da","family":"C\u00e2mara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela Sales Lima","family":"Nascimento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Marcos Matta","family":"Guedes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1006\/expr.1996.0109","article-title":"Trypanosoma Cruzi: IL-10, TNF, IFN-Gamma, and IL-12 Regulate Innate and Acquired Immunity to Infection","volume":"84","author":"Abrahamsohn","year":"1996","journal-title":"Exp. 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