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 journalArticle

51 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)118-128
Number of pages11
JournalNature Immunology
Volume16
Issue number1
DOIs
StatePublished - Dec 18 2014

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T-Lymphocytes
HIV-1
Toll-Like Receptors
RNA Virus Infections
Pattern Recognition Receptors
Virus Diseases
Immune System
Transcription Factors
Down-Regulation
Calcium
Gene Expression

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Dominguez-Villar, M., Gautron, A. S., De Marcken, M., Keller, M. J., & Hafler, D. A. (2014). TLR7 induces anergy in human CD4+ T cells. Nature Immunology, 16(1), 118-128. https://doi.org/10.1038/ni.3036

TLR7 induces anergy in human CD4+ T cells. / Dominguez-Villar, Margarita; Gautron, Anne Sophie; De Marcken, Marine; Keller, Marla J.; Hafler, David A.

In: Nature Immunology, Vol. 16, No. 1, 18.12.2014, p. 118-128.

Research output: Contribution to journalArticle

Dominguez-Villar, M, Gautron, AS, De Marcken, M, Keller, MJ & Hafler, DA 2014, 'TLR7 induces anergy in human CD4+ T cells', Nature Immunology, vol. 16, no. 1, pp. 118-128. https://doi.org/10.1038/ni.3036
Dominguez-Villar M, Gautron AS, De Marcken M, Keller MJ, Hafler DA. TLR7 induces anergy in human CD4+ T cells. Nature Immunology. 2014 Dec 18;16(1):118-128. https://doi.org/10.1038/ni.3036
Dominguez-Villar, Margarita ; Gautron, Anne Sophie ; De Marcken, Marine ; Keller, Marla J. ; Hafler, David A. / TLR7 induces anergy in human CD4+ T cells. In: Nature Immunology. 2014 ; Vol. 16, No. 1. pp. 118-128.
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