IL-10 Producing B Cells Dampen Protective T Cell Response and Allow Infection of the Male Genital Tract

A significant proportion of individuals develop chronic, persistent and recurrent genital tract infections with , which has been attributed to the numerous strategies that the bacterium uses to subvert host immune responses. Animal chlamydia models have demonstrated that protective immune response is mediated by CD4 Th1 cytokine responses. Herein, we demonstrate that early after infecting the male genital tract, triggers the production of IL-10 by splenic and lymph node cells. In addition, triggers IL-6 and TNFα secretion. Data obtained from and experiments revealed B cells as the major IL-10 contributors. Indeed, purified B cells produced high amounts of IL-10 and also exhibited enhanced expression of inhibitory molecules such as CD39, PD-L1 and PD1 after stimulation. experiments performed with sorted cell subsets revealed that Marginal Zone B cells were the main IL-10 producers. and studies using TLR-deficient mice indicated that TLR4 signaling pathway was essential for IL-10 production. In addition, treatments to neutralize IL-10 or deplete B cells indicated that IL-10 and B cells played a significant role in delaying bacterial clearance ability. Moreover, the latter was confirmed by adoptive cell transfer experiments in which the absence of IL-10-producing B cells conferred the host a greater capability to induce Th1 responses and clear the infection. Interestingly, NOD mice, which were the least efficient in clearing the infection, presented much more Marginal Zone B counts and also enhanced TLR4 expression on Marginal Zone B cells when compared to B6 and BALB/c mice. Besides, treatment with antibodies that selectively deplete Marginal Zone B cells rendered mice more capable of inducing enhanced IFNγ responses and clearing the infection. Our findings suggest that B cells play a detrimental role in infection and that activation by innate receptors like TLR4 and IL-10 production by these cells could be used by spp. as a strategy to modulate the immune response establishing chronic infections in susceptible hosts.