Department of Medicine, Division of Infectious Diseases and Immunology
Immunity | Immunology and Infectious Disease | Immunology of Infectious Disease | Infectious Disease | Parasitic Diseases
Toll-like receptors (TLRs) play a central role in macrophage activation and control of parasitic infections. Their contribution to the outcome of Leishmania infection is just beginning to be deciphered. We examined the interaction of Leishmania panamensis with TLRs in the activation of host macrophages. L. panamensis infection resulted in upregulation of TLR1, TLR2, TLR3, and TLR4 expression and induced tumor necrosis factor alpha (TNF-alpha) secretion by human primary macrophages at comparable levels and kinetics to those of specific TLR ligands. The TLR dependence of the host cell response was substantiated by the absence of TNF-alpha production in MyD88/TRIF(-/-) murine bone marrow-derived macrophages and mouse macrophage cell lines in response to promastigotes and amastigotes. Systematic screening of TLR-deficient macrophages revealed that TNF-alpha production was completely abrogated in TLR4(-/-) macrophages, consistent with the increased intracellular parasite survival at early time points of infection. TNF-alpha secretion was significantly reduced in macrophages lacking endosomal TLRs but was unaltered by a lack of TLR2 or MD-2. Together, these findings support the participation of TLR4 and endosomal TLRs in the activation of host macrophages by L. panamensis and in the early control of infection.
Toll-Like Receptors, Macrophages, Leishmania (Viannia) panamensis
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Copyright © 2011, American Society for Microbiology. Publisher PDF posted after 6 months as allowed by the publisher's author rights policy at https://journals.asm.org/content/statement-author-rights.
DOI of Published Version
Infect Immun. 2011 Jul;79(7):2871-9. doi: 10.1128/IAI.01388-10. Epub 2011 Apr 25. Link to article on publisher's site
Infection and immunity
Gallego C, Golenbock DT, Gomez MA, Saravia NG. (2011). Toll-like receptors participate in macrophage activation and intracellular control of Leishmania (Viannia) panamensis. Infectious Diseases and Immunology Publications. https://doi.org/10.1128/IAI.01388-10. Retrieved from https://escholarship.umassmed.edu/infdis_pp/378