Open AccessDistinct Roles for MyD88 and Toll-Like Receptor 2 during Leishmania braziliensis Infection in Mice
Author(s) -
Diego A. Vargas-Inchaustegui,
Wendy Tai,
Xin Luo,
Alison Hogg,
David B. Corry,
Lynn Soong
Publication year - 2009
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00154-09
Subject(s) - biology , tlr2 , leishmania braziliensis , immunology , leishmania major , priming (agriculture) , immunity , innate immune system , leishmania , toll like receptor , immune system , microbiology and biotechnology , parasite hosting , cutaneous leishmaniasis , leishmaniasis , botany , germination , world wide web , computer science
We have previously reported thatLeishmania braziliensis infection can activate murine dendritic cells (DCs) and upregulate signaling pathways that are essential for the initiation of innate immunity. However, it remains unclear whether Toll-like receptors (TLRs) are involved inL. braziliensis -mediated DC activation. To address this issue, we generated bone marrow-derived DCs from MyD88−/− and TLR2−/− mice and examined their responsiveness to parasite infection. While wild-type DCs were efficiently activated to produce cytokines and prime naïve CD4+ T cells,L. braziliensis -infected MyD88−/− DCs exhibited less activation and decreased production of interleukin-12 (IL-12) p40. Furthermore, MyD88−/− mice were more susceptible to infection in that they developed larger and prolonged lesions compared to those in control mice. In sharp contrast, the lack of TLR2 resulted in an enhanced DC activation and increased IL-12 p40 production after infection. As such,L. braziliensis -infected TLR2−/− DCs were more competent in priming naïve CD4+ T cells in vitro than were their controls, findings which correlated with an increased gamma interferon production in vivo and enhanced resistance to infection. Our results suggest that while MyD88 is indispensable for the generation of protective immunity toL. braziliensis , TLR2 seems to have a regulatory role during infection.