IL-9-producing cells promote Th1 responses against Mycobacterium tuberculosis. (P3015)

Abstract

Abstract IFNγ-secreting cells are critical in the defense against M. tuberculosis (Mtb) infection, but other cells might be required to eradicate the pathogen. IL-9-producing cells were reported to be involved in inflammation and immune diseases, but their role during tuberculosis remains to be clarified. Here we analyzed the involvement of IL-9-secreting cells in the immunity of patients with active disease. We demonstrated that Mtb induced a marked expansion of CD4 IL-9+ cells in peripheral blood from tuberculosis patients. After antigen stimulation, patients with robust Th1 responses to Mtb (high responders) produced higher amounts of IL-9 compared to those with weak Th1 responses (low responders) and a direct significant correlation between IL-9 and IFNγ production against Mtb was detected. To investigate the role of the IL-9 secreted by those lymphocytes, we inhibited IL-9 expression with siRNA, which significantly diminished the production of IFNγ against Mtb. Addition of IL-9 markedly increased the secretion of IFNγ against Mtb, even in low responders. Furthermore, treatment with IL-9 inhibited Mtb-induced apoptosis of IFNγ+ cells, enhancing the survival of the cells. Finally, by studying the effect of neutralizing IL-9 antibodies on polarized Th9 cells, we confirmed that IL-9 participates in the up-regulation of IFNγ production against Mtb. Thus, our results indicate that IL-9 enhances Th1 responses during tuberculosis promoting the cell-mediated immunity to the pathogen.