Authors agree to be accountable for all aspects of the work in terms of accuracy or integrity and other related aspects
Authors agree to be accountable for all aspects of the work in terms of accuracy or integrity and other related aspects. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments We thank Paula Abadie, Pilar Crespo, Gabriela Furlan, and Laura Gatica for technical assistance. 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 IFN responses and clearing the infection. Our findings suggest that Taxifolin B cells play a detrimental role in infection Taxifolin 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. Keywords: infection has increased dramatically over the past 30 years in both developed and developing countries (2). Approximately 75% of infections in women and up to 50% of those in men are asymptomatic; thus, they often remain undiagnosed and/or untreated facilitating the development of chronic infections and the spread of the pathogen (1, 3). Clinical manifestations of chlamydial infections in women include urethritis, bartholinitis, cervicitis, and upper genital tract infection (including endometritis, salpingo-oophoritis, and pelvic inflammatory disease), which if left untreated can lead to severe reproductive complications (3, 4). In men, infects urethra being a major cause of male urethritis, which usually constitutes an acute episode of an underlying chronic silent infection affecting the prostate, seminal vesicles, epididymis, and testis (5C7). In both, female and male genital tract infections, stimulates a complex array of host innate and adaptive immune responses (6, 8C10). It has been demonstrated that innate immune receptors such as TLR4, Taxifolin TLR2, and others mediate the recognition of chlamydial molecular patterns. Innate immune cells rapidly recognize and limit the infection, and ultimately influence the outcome through the modulation of the adaptive immune response (11). Existing literature clearly points out CD4+ T cells, particularly Th1cells, as the major immune effectors for bacterial clearance in the genital tract (12C14). In addition, host regulatory pathways also become activated to limit the magnitude of excessive immunopathology (15). Although effector innate and adaptive immune responses are induced, they often fail to clear the infection or prevent subsequent re-infections (16). In fact, the specific adaptive immune response often fails to prevent re-infections, which are very frequent (3, 17). This has been attributed to several immunoevasion strategies of interferes with the induction of apoptosis protecting itself against the immune response (20), and modulates host cytokine production skewing immune responses (21). Noteworthy, induces the production of IL-10, a potent cytokine that can facilitate pathogen survival by negatively regulating both innate and adaptive host responses (22C24). In this regard, we recently reported higher IL-10 production and delayed bacterial clearance in NOD mice after male genital tract infection (25). Multiple cell types are capable of producing IL-10 during infection including activated macrophages, dendritic cells, keratinocytes, T and B lymphocytes (24C27). However, the contribution of IL-10 producing cells to modulate the quality, magnitude Rabbit polyclonal to PON2 and direction of the host immune response in infection has been scarcely studied. In the present report, comparing different mice strains and different time points we demonstrate that splenic and prostate-draining lymph node cells from infected mice produce high amounts of IL-10 in response to stimulation Taxifolin early after infection through the engagement of innate immune receptors. experiments showed that purified B cells and MZB.