TLR9/MyD88/TRIF signaling activates host immune inhibitory CD200 in Leishmania infection

Autor(es)

Sauter, Ismael P. ^[1] ; Madrid, Katerine G. ^[1] ; de Assis, Josiane B. ^[2] ; Sa-Nunes, Anderson ^[2] ; Torrecilhas, Ana C. ^[3] ; Staquicini, I, Daniela ; Pasqualini, Renata ^{[4, 5]} ; Arap, Wadih ^{[6, 7]} ; Cortez, Mauro ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Parasitol, BR-05508 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Dept Pharmaceut Sci, Sao Paulo - Brazil

^[4] Staquicini, Daniela, I, Rutgers New Jersey Med Sch, Dept Radiat Oncol, Rutgers Canc Inst New Jersey, Newark, NJ 07730 - USA

^[5] Staquicini, Daniela, I, Rutgers New Jersey Med Sch, Dept Radiat Oncol, Div Canc Biol, Newark, NJ 07730 - USA

^[6] Rutgers New Jersey Med Sch, Rutgers Canc Inst New Jersey, Dept Med, Newark, NY 07730 - USA

^[7] Rutgers New Jersey Med Sch, Div Hematol Oncol, Dept Med, Newark, NY 07730 - USA

• Tipo de documento: Artigo Científico
• Fonte: JCI INSIGHT; v. 4, n. 10 MAY 16 2019.
• Citações Web of Science: 0

Resumo

Virulent protozoans named Leishmania in tropical and subtropical areas produce devastating diseases by exploiting host immune responses. Amastigotes of Leishmania amazonensis stimulate macrophages to express CD200, an immunomodulatory ligand, which binds to its cognate receptor (CD200R) and inhibits the inducible nitric oxide synthase and nitric oxide (iNOS/NO) signaling pathways, thereby promoting intracellular survival. However, the mechanisms underlying CD200 induction in macrophages remain largely unknown. Here, we show that phagocytosis-mediated internalization of L. amazonensis amastigotes following activation of endosomal TLR9/MyD88/TRIF signaling is critical for inducing CD200 in infected macrophages. We also demonstrate that Leishmania microvesicles containing DNA fragments activate TLR9-dependent CD200 expression, which inhibits the iNOS/NO pathway and modulates the course of L. amazonensis infection in vivo. These findings demonstrate that Leishmania exploits TLR-signaling pathways not only to inhibit macrophage microbicidal function, but also to evade host systemic immune responses, which has many implications in the severity of the disease. (AU)

• Processo FAPESP: 12/24105-3 - Imunobiologia de Leishmania spp.: estudo do papel de CD200 e biogênese do vacúolo parasitóforo em células fagocíticas infectadas por Leishmania
• Beneficiário: Mauro Javier Cortez Véliz
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores