Role of CD8+T cells in the host response to Chlamydia

Abstract

Chlamydia infections constitute a major public health problem. Although multiple arms of the immune system participate in the control of Chlamydia in infected hosts, T lymphocytes are essential. This review focuses on the roles that CD8 + T cells may play in immunoprotection and immunopathology following recognition of Chlamydia-infected cells. KeywordsChlamydia; CD8 + T cells IntroductionMembers of the Chlamydiaceae family are obligate intracellular gram-negative bacteria that include the human pathogens Chlamydia trachomatis (Ct) and Chlamydia pneumoniae (Cpn). While Ct is responsible for ocular and sexually transmitted diseases that can result in blindness and infertility, Cpn is a common cause of upper respiratory infections and pneumonia and has been associated with several chronic inflammatory conditions such as atherosclerosis and chronic obstructive pulmonary disease (COPD) [1][2][3]. When diagnosed early, Chlamydia infections can be treated with antibiotics. However, the high costs required to identify and treat individuals with mild or no symptoms limits the feasibility of this control strategy. Moreover, hosts can remain chronically infected despite chemotherapy, and some antibiotics may induce chlamydial persistence [4]. Thus, development of safe and effective vaccines represents a cost-effective approach that would have a greater impact on the high prevalence of Chlamydia infections and the prevention of severe long-term sequelae.Like all chlamydiae, Ct and Cpn have a unique biphasic developmental cycle alternating between an infectious metabolically inert elementary body (EB) and a replicating metabolically active reticulate body (RB). After entry into susceptible cells such as epithelial cells, macrophages, endothelial and smooth muscle cells, the EB remains within a nonacidified vacuole known as an inclusion, where it differentiates into a RB, which replicates by binary fission. The generated progeny differentiate back into EBs that are then released upon host cell lysis to infect other cells. Under certain conditions, however, Chlamydia enters a persistent non-replicating stage but remains capable of resuming a productive cycle when the adverse *Corresponding author. Current mailing address: Intercell AG, Campus Vienna Biocenter 6, 1030 Wien, Austria. Phone: +43-1-20620-174. Fax: +43-1-20620-805. E-mail: bwizel@intercell.com. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Evidence of a role for CD8 + T cells in the immune control of ChlamydiaAn intact T cell compartment is required for resistance against Chlamydia infection. T ...

Genital Chlamydia trachomatis: Understanding the Roles of Innate and Adaptive Immunity in Vaccine Research

“…ϩ T cells are known to migrate to the infection site, and both human and mouse CD8 ϩ T cells have been shown to destroy cells that have been infected with Chlamydia (94). A recent study by Murthy and colleagues showed that wt and CD8 ϩ T knockout mice displayed similar clearances of C. muridarum following vaginal chlamydial challenge (95).…”

Views of immunology: effector T cells

“…Studies of mice depleted of IFN-c implicate an important role in host defense to Chlamydia species in various mouse models as well (42). While multiple cell types produce IFN-c within the context of Chlamydia infection, including both CD4 + and CD8 + T cells, CD8 + T cells may serve as the most important source of this cytokine (63). For example, CD8 + T cells derived from wildtype mice, but not IFN-c-deficient mice protected naive mice from infection with C. trachomatis (64).…”

OT-1 mice display minimal upper genital tract pathology following primary intravaginalChlamydia muridaruminfection

“…The findings of this study have important implications. (1) Previous reports suggest that certain CD8 + T cell clones that recognize specific chlamydial epitopes may assist in bacterial clearance (Wizel et al, 2008) and thus may be suitable as vaccine candidates. Our findings do not exclude this possibility; however, they suggest the need to exercise due diligence in applying such immune responses for the The number of normal oviducts or uterine horns (numerator) and the total number of oviducts or uterine horns evaluated (denominator) have been indicated in parentheses on the x-axis.…”