<div><p>STAT3 is a master regulator of the immune responses. Here we show that <i>M</i>. <i>tuberculosis</i>-infected <i>stat3</i><sup><i>fl/fl</i></sup> <i>lysm cre</i> 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 <i>stat3</i><sup><i>fl/fl</i></sup> <i>lysm cre</i> 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 <i>stat3</i><sup><i>fl/fl</i></sup> <i>lysm cre</i> 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, <i>socs3</i><sup><i>fl/fl</i></sup> <i>cd11c cre</i> mice deficient of SOCS3 in DCs showed increased susceptibility to <i>M</i>. <i>tuberculosis</i> 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 <i>M</i>. <i>tuberculosis</i>.</p></div
