Role of Regulatory T cells in Leishmania major infection

描述（由申请人提供）：潜伏感染是人类疾病的重要组成部分。延迟的实现为主机提供了明显的好处。除了阻止微生物介导的损伤外，我们还表明潜伏感染对于维持对再感染的免疫力至关重要。另一方面，潜伏期允许疾病重新激活的可能性，并促进微生物扩散到新的宿主。因此，潜伏期对宿主和病原体都有利。通过小鼠模型，我们已经证明CD4+CD25+调节性T细胞（Treg）对于潜伏性皮肤感染利什曼原虫的发展和维持是必不可少的。Treg迅速积聚在感染Lm的部位，抑制免疫反应完全消灭寄生虫的能力。这种潜伏期的实现与感染部位Treg积累的动态密切相关。

DESCRIPTION (provided by the applicant): Latent infections are an essential part of the human condition. The achievement of latency provides clear benefits to the host. In addition to halting microbe-mediated damage, we have shown that latent infection can be essential for the maintenance of immunity to reinfection. On the other hand, latency allows for the possibility of disease reactivation, and facilitates microbial dispersal to new hosts. Latency can thus benefit both host and pathogen. Using murine models, we have shown that CD4+CD25+ regulatory T cells (Treg) are essential for the development and maintenance of latent cutaneous infection Leishmania major. Treg rapidly accumulate at sites of infection with Lm, suppressing the ability of the immune response to completely eliminate the parasite. This achievement of latency is tightly linked to the dynamics of Treg accumulation at the site of infection. The inter-related hypotheses underlying these studies are that: (a) host/parasite interactions in infected icroenvironments drive the specific migration of Treg to such sites; (b) the dynamics of Treg accumulation at sites of infection are prime determinants of the efficiency of pathogen clearance and the development of concomitant immunity; (c) Treg regulate local immune responses by modulating the function of both APC and effector T cells; and (d) Treg modulate APC function largely though the release of IL-10. The goal of the current proposal is to define the mechanisms by which Treg modulate the immune response to leishmanial infection. We aim to: (1) Define the mechanisms underlying the specific recruitment of Treg to sites of infection with L. major; and (2) Determine the mechanisms underlying Treg-mediated modulation of immune responses to L. major both in vitro and in vivo.