The Role of the Immune Response in Chlamydia trachomatis Infection of the Male Genital Tract: A Double-Edged Sword

Abstract

Chlamydia trachomatis (CT) is the most prevalent bacterial sexually transmitted infection in the world, with more than 100 million cases reported annually. While there have been extensive studies into the adverse effects that CT infection has on the female genital tract, and on the subsequent ability of these women to conceive, studies into the consequences on male fertility have been limited and controversial. This is in part due to the asymptomatic nature of the infection, where it is estimated that 50% of men with Chlamydia fail to show any symptoms. It is accepted, however, that acute and/or persistent CT infection is the causative agent for conditions such as urethritis, epididymitis, epididymo-orchitis, and potentially prostatitis. As with most infections, the immune system plays a fundamental role in the body’s attempts to eradicate the infection. The first and most important immune response to Chlamydia infection is a local one, whereby immune cells such as leukocytes are recruited to the site of infections, and subsequently secrete pro-inflammatory cytokines and chemokines such as interferon gamma. Immune cells also work to initiate and potentiate chronic inflammation through the production of reactive oxygen species (ROS), and the release of molecules with degradative properties including defensins, elastase, collagenase, cathespins, and lysozyme. This long-term inflammation can lead to cell proliferation (a possible precursor to cancer), tissue remodeling, and scarring, as well as being linked to the onset of autoimmune responses in genetically disposed individuals. This review will focus on the ability of the immune system to recognize and clear acute and persistent chlamydial infections in the male genital tract, and on the paradoxical damage that chronic inflammation resulting from the infection can cause on the reproductive health of the individual.

Chlamydia trachomatis Is Resistant to Inclusion Ubiquitination and Associated Host Defense in Gamma Interferon-Primed Human Epithelial Cells

“…No vaccine is currently available, and recurring, repeat, or chronic infections are frequent. The inefficacy of our immune system to clear C. trachomatis infections and its deficiency in establishing protective immune memory demonstrate that C. trachomatis can undermine human immunity (2–4, 8). However, how C. trachomatis escapes clearance by both innate and adaptive immune responses of its human host is poorly understood.…”

“…According to the World Health Organization, an estimated 100 million individuals are infected per annum (1). Many of these infections lead to disease and irreparable pathologies; C. trachomatis infections frequently result in urethritis in men and pelvic inflammatory disease, tubal factor infertility, and ectopic pregnancies in women (2–4). C. trachomatis -associated diseases in women are due to extensive pathogen exposure stemming from chronic, recurring, or repeat infections, all indicative of an inability of the human immune system to promptly sterilize C. trachomatis infections or to establish effective immune memory.…”

“…C. trachomatis -associated diseases in women are due to extensive pathogen exposure stemming from chronic, recurring, or repeat infections, all indicative of an inability of the human immune system to promptly sterilize C. trachomatis infections or to establish effective immune memory. The failure of our immune system to protect against C. trachomatis infections is likely the consequence of active or passive immune evasion by this stealth pathogen (2–8). …”

Role of Oxidative Stress and Chlamydia trachomatis in Infertile Women with Anti-Zona Pellucida Autoantibodies

“…In the reproductive system, the presence of inflammatory cytokines (TNF-α, IFN-γ, IL-1) and the high levels of free radicals may damage biological molecules by oxidation and chemically modifying cell proteins which consequently can change their antigenicity and therefore become implicated in immunological deleterious reactions associated with inflammatory and/or autoimmune injury [8]. An altered protein function and the presence of circulating autoantibodies to new epitopes could block some membrane surface antigens with a receptor function in the reproductive system.…”

A characteristic of polymorphic membrane protein F of Chlamydia trachomatis isolated from male urogenital tracts in Japan

“…Obligate intracellular bacterium Chlamydia trachomatis is a causative agent of sexually transmitted diseases, leading to serious complications involving infertility (e.g., in females: ductal obstruction, pelvic inflammatory disease, tubal occlusion; in males: testicular atrophy, epididymitis, orchitis) [1][2][3][4][5][6]. Chlamydial infection occurs similarly in both men and women.…”