Open AccessSTAT3 expression by myeloid cells is detrimental for the T- cell-mediated control of infection with Mycobacterium tuberculosis
Author(s) -
Yu Gao,
Juan I. Basile,
Cajsa Classon,
Dolores GavierWidén,
Akihiko Yoshimura,
Berit Carow,
Martı́n E. Rottenberg
Publication year - 2018
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1006809
Subject(s) - biology , cd11c , mycobacterium tuberculosis , immune system , secretion , socs3 , myeloid , priming (agriculture) , t cell , immunology , cytokine , microbiology and biotechnology , stat3 , tuberculosis , medicine , signal transduction , biochemistry , botany , germination , pathology , gene , phenotype
STAT3 is a master regulator of the immune responses. Here we show that M . tuberculosis -infected stat3 fl/fl lysm 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 stat3 fl/fl lysm 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 stat3 fl/fl lysm 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, socs3 fl/fl cd11c 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 .