The cGAS/STING Pathway Is Important for Dendritic Cell Activation but Is Not Essential to Induce Protective Immunity against Mycobacterium tuberculosis Infection

Fabio V. Marinho, Sulayman Benmerzoug, Stephanie Rose, Priscila C. Campos, João T. Marques, André Báfica, Glen N Barber, Bernhard Ryffel, Sergio C. Oliveira, Valerie F.J. Quesniaux

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Mycobacterium tuberculosis (Mtb) infection remains a major public health concern. The STING (stimulator of interferon genes) pathway contributes to the cytosolic surveillance of host cells. Most studies on the role of STING activation in Mtb infection have focused on macrophages. Moreover, a detailed investigation of the role of STING during Mtb infection in vivo is required. Here, we deciphered the involvement of STING in the activation of dendritic cells (DCs) and the host response to Mtb infection in vivo. In DCs, this adaptor molecule was important for Ifn-β expression and IL-12 production as well as for the surface expression of the activation markers CD40 and CD86. We also documented that Mtb DNA induces STING activation in murine fibroblasts. In vivo Mtb aerogenic infection induced the upregulation of the STING and cGAS (cyclic GMP-AMP synthase) genes, and Ifn-β pulmonary expression was dependent on both sensors. However, mice deficient for STING or cGAS presented a similar outcome to wild-type controls, with no major alterations in body weight gain, bacterial burden, or survival. Lung inflammation, proinflammatory cytokine production, and inflammatory cell recruitment were similar in STING- and cGAS-deficient mice compared to wild-type controls. In summary, although the STING pathway seems to be crucial for DC activation during Mtb infection, it is dispensable for host protection in vivo.

Original languageEnglish (US)
Pages (from-to)237-250
Number of pages14
JournalJournal of Innate Immunity
DOIs
StateAccepted/In press - May 23 2018

Fingerprint

GMP synthase (glutamine-hydrolyzing)
Mycobacterium Infections
Mycobacterium tuberculosis
Dendritic Cells
Interferons
Immunity
Genes
Transcriptional Activation
cyclic guanosine monophosphate-adenosine monophosphate
Interleukin-12

Keywords

  • cGAS
  • Dendritic cells
  • Mycobacterium tuberculosis
  • STING

ASJC Scopus subject areas

  • Immunology and Allergy

Cite this

The cGAS/STING Pathway Is Important for Dendritic Cell Activation but Is Not Essential to Induce Protective Immunity against Mycobacterium tuberculosis Infection. / Marinho, Fabio V.; Benmerzoug, Sulayman; Rose, Stephanie; Campos, Priscila C.; Marques, João T.; Báfica, André; Barber, Glen N; Ryffel, Bernhard; Oliveira, Sergio C.; Quesniaux, Valerie F.J.

In: Journal of Innate Immunity, 23.05.2018, p. 237-250.

Research output: Contribution to journalArticle

Marinho, Fabio V. ; Benmerzoug, Sulayman ; Rose, Stephanie ; Campos, Priscila C. ; Marques, João T. ; Báfica, André ; Barber, Glen N ; Ryffel, Bernhard ; Oliveira, Sergio C. ; Quesniaux, Valerie F.J. / The cGAS/STING Pathway Is Important for Dendritic Cell Activation but Is Not Essential to Induce Protective Immunity against Mycobacterium tuberculosis Infection. In: Journal of Innate Immunity. 2018 ; pp. 237-250.
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