{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T23:20:45Z","timestamp":1794266445340,"version":"4.9.0"},"reference-count":78,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In livers of susceptible but self-curing C57BL\/6 mice, intracellular\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania donovani<\/jats:named-content>\n            infection enhanced Toll-like receptor 4 (TLR4) and TLR2 gene expression. In the liver, infected TLR4\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice showed reduced gamma interferon (IFN-\u03b3), tumor necrosis factor (TNF), and inducible nitric oxide synthase (iNOS) mRNA expression, higher-level and slowly resolving infection, delayed granuloma formation, and little response to low-dose chemotherapy; in serum, the ratio of IFN-\u03b3 to interleukin 10 (IL-10) activity was decreased by 50%. In contrast, in TLR2\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice, control of liver infection, parasite killing, and granuloma assembly were accelerated and chemotherapy's efficacy enhanced. In livers of infected TLR2\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice, mRNA expression was not increased for inflammatory cytokines or iNOS or decreased for IL-10; however, the serum IFN-\u03b3\/IL-10 ratio was increased 6.5-fold and minimal responses to IL-10 receptor blockade suggested downregulated IL-10. In established infection in wild-type mice, blockading TLR2 induced parasite killing and triggering TLR4 strengthened resistance and promoted chemotherapy's effect. Thus, in experimental\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">L. donovani<\/jats:named-content>\n            infection in the liver, TLR4 signaling upregulates and TLR2 signaling downregulates macrophage antileishmanial activity, making both receptors potential therapeutic targets in visceral leishmaniasis for engagement (TLR4) or blockade (TLR2).\n          <\/jats:p>","DOI":"10.1128\/iai.01468-12","type":"journal-article","created":{"date-parts":[[2013,4,16]],"date-time":"2013-04-16T01:07:53Z","timestamp":1366074473000},"page":"2318-2326","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["Regulatory Actions of Toll-Like Receptor 2 (TLR2) and TLR4 in Leishmania donovani Infection in the Liver"],"prefix":"10.1128","volume":"81","author":[{"given":"Henry W.","family":"Murray","sequence":"first","affiliation":[{"name":"Departments of Medicine, Weill Cornell Medical College, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Weill Cornell Medical College, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Immunology and Microbiology, Weill Cornell Medical College, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanitha S.","family":"Raman","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Institute, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G.","family":"Reed","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Institute, Seattle, Washington, 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