Abstract
The recognition of microbial patterns by Toll-like receptors (TLRs) is critical for activation of the innate immune system. Although TLRs are expressed by human CD4+ T cells, their function is not well understood. Here we found that engagement of TLR7 in CD4+ T cells induced intracellular calcium flux with activation of an anergic gene-expression program dependent on the transcription factor NFATc2, as well as unresponsiveness of T cells. As chronic infection with RNA viruses such as human immunodeficiency virus type 1 (HIV-1) induces profound dysfunction of CD4+ T cells, we investigated the role of TLR7-induced anergy in HIV-1 infection. Silencing of TLR7 markedly decreased the frequency of HIV-1-infected CD4+ T cells and restored the responsiveness of those HIV-1 + CD4+ T cells. Our results elucidate a previously unknown function for microbial pattern-recognition receptors in the downregulation of immune responses.
Original language | English (US) |
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Pages (from-to) | 118-128 |
Number of pages | 11 |
Journal | Nature Immunology |
Volume | 16 |
Issue number | 1 |
DOIs | |
State | Published - Dec 18 2015 |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology