Cutting edge: diminished T cell TLR expression and function modulates the immune response in human filarial infection.
Patent lymphatic filariasis is characterized by profound Ag-specific T cell hyporesponsiveness with impaired IFN-gamma and IL-2 production. Because T cells have been shown to express a number of TLR and to respond to TLR ligands, we hypothesized that diminished T cell TLR function could partially account for the T cell hyporesponsiveness in filariasis. T cells expressed TLR1, TLR2, TLR4, and TLR9, and the baseline expression of TLR1, TLR2, and TLR4, but not TLR9 was significantly lower in T cells of the filarial-infected individuals compared with the uninfected individuals (both endemic and nonendemic). TLR function was significantly diminished in the T cells of filarial-infected individuals based on decreased T cell activation/cytokine production in response to TLR ligands. Thus, diminished expression and function of T cell TLR is a novel mechanism underlying T cell immune tolerance in lymphatic filariasis.
Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. sbabu@niaid.nih.gov
Subash
S
Babu
Carla P
CP
Blauvelt
V
V
Kumaraswami
Thomas B
TB
Nutman
D000818:Animals; D002469:Cell Separation; D005368:Filariasis / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D005370:Filarioidea / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007372:Interferons / Q000378:metabolism; D008024:Ligands; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism*
D008024:Ligands; D051193:Toll-Like Receptors; D007372:Interferons