Role of regulatory T cells in controlling chlamydia-induced immunity and inflammation

Chlamydia species infect the mucosal epithelium of the ocular, respiratory and genital track causing a wide spectrum of diseases including trachoma (caused by corneal scarring), infertility (caused by fallopian tube scarring) and many other chronic inflammatory conditions worldwide. Clearly, a comprehensive understanding about the disease process and host immune responses towards this group of intracellular bacteria is urgently needed for developing prophylactic and therapeutic interventions for combating ubiquitous chlamydial infection and Chlamydia-associated sequelae. The critical role of regulatory T cells in controlling immune homeostasis has been firmly established now. The natural occurring T regulatory (nTreg) cells are a subset of Treg cells that play a dominant role in preventing autoimmune diseases by suppressing activation of auto-reactive lymphocytes. Emerging evidence indicates that nTreg cells also respond to infectious agents and regulate the magnitude of immune responses towards invading pathogens. While nTreg involvement may protect the host from collateral tissue damage associated with heightened immune responses, nTreg activity may also lead to immune dysfunction resulting persistent infection and subsequent tissue damage. The specific involvement of nTreg in infections appears to be determined largely by the host genetic background and the specific pathogen involved. In this proposal, various in vitro experimentations and animal models that mimic respiratory infections in humans will be used to examine the specific role of nTreg in controlling Chlamydia-induced immunity and inflammation. The knowledge attained from these studies will provide fundamental understanding about the role of nTreg and the network between nTreg cells and other immune cellular components, which will be essential for devising prophylactic and therapeutic strategies against chlamydial infection by manipulating nTreg activity.