Chlamydia muridarum dampens the induction of protective Th1 immune responses by inducing IL10-producing B cells

SANCHEZ, LR; GODOY, GJ; GOROSITO SERRAN, M; MOTRICH, RD; GRUPPI, A; RIVERO, VE

Buenos Aires

Congreso; LXIII Reunión Anual de SAI, I Meeting LASID-SAI-FAIC, IV Meeting LASID, y II Meeting FAIC.; 2015

Sociedad Argentina de Inmunologia

Background: Chlamydia trachomatis is the most prevalent sexually transmitted bacterial infection worldwide. It has been postulated that Chlamydia spp. would evade host defenses through different strategies, e.g. the induction of anti-inflammatory cytokines like IL10. Herein, we evaluated the role of IL10-producing B cells in a model of male genital tract (MGT) infection with Chlamydia muridarum (Cm), a serovar that infects rodents and produces a similar disease to that observed in humans.Methods: Male NOD mice were inoculated with Cm in the meatus urethra and then euthanized at different times post infection. Bacterial burden in the MGT organs and cytokines produced by Cm-stimulated spleen or lymph node mononuclear cells (MNC) were analyzed.Results: qPCR analyses revealed higher bacterial burdens in prostate than in urethral tissues from infected NOD mice (p<0.05). High levels of IL10 and low amounts of IL17 and IFNγ were detected in culture supernatants of Cm-stimulated MNC from infected mice (p<0.05). FACS analysis identified B cells as the major IL10-producing cell population. In addition, FACS purified B cells secreted high amounts of IL10 after in vitro stimulation with Cm. Moreover, IL10+CD19+ B cells revealed a phenotype compatible with B1a (CD19+CD1d+CD5+) and marginal zone (CD19+CD21+CD23+) B lymphocytes. After blocking IL10 or depleting B cells from infected NOD mice, decreased prostate bacterial burdens and increased spleen frequencies of CD3+IFNγ+ cells were observed (p<0.05).Conclusions: Our results suggests that Cm infection induces IL10-producing B cells, which in turn modulate the induction of protective Th1 responses, allowing Cm chronic persistence in the MGT.