TLR7 induces anergy in human CD4+ T cells

Margarita Dominguez-Villar, Anne Sophie Gautron, Marine De Marcken, Marla J. Keller, David A. Hafler

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


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 languageEnglish (US)
Pages (from-to)118-128
Number of pages11
JournalNature Immunology
Issue number1
StatePublished - Dec 18 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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