STAT3 expression by myeloid cells is detrimental for the T- cell-mediated control of infection with Mycobacterium tuberculosis

Yu Gao, Juan Ignacio Basile, Cajsa Classon, Dolores Gavier-Widen, Akihiko Yoshimura, Berit Carow, Martin E. Rottenberg

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

STAT3 is a master regulator of the immune responses. Here we show that M. tuberculosis-infected stat3fl/fllysm cre mice, defective for STAT3 in myeloid cells, contained lower bacterial load in lungs and spleens, reduced granuloma extension but higher levels of pulmonary neutrophils. STAT3-deficient macrophages showed no improved control of intracellular mycobacterial growth. Instead, protection associated to elevated ability of stat3fl/fllysm cre antigen-presenting cells (APCs) to release IL-6 and IL-23 and to stimulate IL-17 secretion by mycobacteria-specific T cells. The increased IL-17 secretion accounted for the improved control of infection since neutralization of IL-17 receptor A in stat3fl/fllysm cre mice hampered bacterial control. APCs lacking SOCS3, which inhibits STAT3 activation via several cytokine receptors, were poor inducers of priming and of the IL-17 production by mycobacteria-specific T cells. In agreement, socs3fl/flcd11c cre mice deficient of SOCS3 in DCs showed increased susceptibility to M. tuberculosis infection. While STAT3 in APCs hampered IL-17 responses, STAT3 in mycobacteria-specific T cells was critical for IL-17 secretion, while SOCS3 in T cells impeded IL-17 secretion. Altogether, STAT3 signalling in myeloid cells is deleterious in the control of infection with M. tuberculosis.

Original languageEnglish
Article numbere1006809
JournalPLoS Pathogens
Volume14
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1

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Interleukin-17
Myeloid Cells
Infection Control
Mycobacterium tuberculosis
T-Lymphocytes
Antigen-Presenting Cells
Mycobacterium
Interleukin-17 Receptors
Interleukin-23
Lung
Cytokine Receptors
Bacterial Load
Granuloma
Interleukin-6
Neutrophils
Spleen
Macrophages
Growth

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

STAT3 expression by myeloid cells is detrimental for the T- cell-mediated control of infection with Mycobacterium tuberculosis. / Gao, Yu; Basile, Juan Ignacio; Classon, Cajsa; Gavier-Widen, Dolores; Yoshimura, Akihiko; Carow, Berit; Rottenberg, Martin E.

In: PLoS Pathogens, Vol. 14, No. 1, e1006809, 01.01.2018.

Research output: Contribution to journalArticle

Gao, Yu ; Basile, Juan Ignacio ; Classon, Cajsa ; Gavier-Widen, Dolores ; Yoshimura, Akihiko ; Carow, Berit ; Rottenberg, Martin E. / STAT3 expression by myeloid cells is detrimental for the T- cell-mediated control of infection with Mycobacterium tuberculosis. In: PLoS Pathogens. 2018 ; Vol. 14, No. 1.
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