Immune Privilege and Inflammation of the Testis

Abstract

Immune cells are found in considerable numbers within the normal, unaffected testes of mammals, including humans. Located in the interstitial compartment, they are implicated in the mechanisms that make the testis an immunologically privileged site where germ cells are protected from autoimmune attack and foreign tissue grafts may survive for extended periods of time. With regard to normal development and function of the testis, both pro- and antiinflammatory cytokines have been shown to play an important regulatory role. The testicular environment, however, does not preclude immune activation resulting in inflammatory reactions and potential damage. In experimental animals, active immunization with testicular tissue or adoptive transfer of specific T lymphocytes causes autoimmune orchitis. In men, infection and inflammation of the reproductive tract including the testes are widely accepted as important etiological factors of infertility. Whereas symptomatic orchitis due to bacterial or viral infections is considered to be rare, a high prevalence of asymptomatic testicular inflammatory reactions could be demonstrated among infertile males. Despite the patchy distribution of the lesions, inflammation is associated with disruption of testicular function, i.e. spermatogenesis. The pattern of lymphocyte infiltration and concomitant damage of seminiferous tubules supports the concept that activation of autoreactive T cells is involved.

Testosterone Replacement Effectively Inhibits the Development of Experimental Autoimmune Orchitis in Rats: Evidence for a Direct Role of Testosterone on Regulatory T Cell Expansion

“…In most cases, inflammation involves also the epididymis, resulting in a combined epididymo-orchitis (4). Whereas acute testicular inflammation is symptomatic and mainly related to infection, the subacute, or chronic, form of the disease is predominately asymptomatic (4)(5)(6). It should be noted that although the acute phase of the disease, which is the consequence of infection, can be successfully treated with antibiotics and antiphlogistics, the inflammatory reaction is more insidious in that it can continue undetected in both testes slowly undermining testicular function (4,(7)(8)(9)(10).…”

The predominance of one of the SR-BI isoforms is associated with increased esterified cholesterol levels not apoptosis in mink testis

“…Spontaneous AIO has been documented in human, dog, mink, and rat (35). The incidence of inflammation of the testis is high in infertile males, and testicular inflammation has been identified as a cause of infertility, although symptomatic orchitis caused by bacterial or viral infections is a rare occurrence in men (36). Immunological male infertility is associated with pathological features that resemble granulomatous orchitis, with inflammation of the testis and persistent infertility documented in infertile mink with spontaneous AIO (35).…”

Testicular innate immune defense against bacteria

“…Hence, it is almost certain that genital tract inflammation/infection including the chronic form contributes to a larger extent to the cohort of patients with "idiopathic" infertility (Schuppe & Meinhardt, 2005;Haidl et al, 2008). Until now, however, the clinical identification of chronic genital tract inflammation/infection has been hampered by the lack of symptoms and non-invasive diagnostic tools.…”

“…It is therefore somewhat paradoxical that microorganisms can (Fijak & Meinhardt, 2006). The direct pathologic effects resulting from the bacterial invasion are often aggravated by the inflammatory process (Schuppe & Meinhardt, 2005;Girling & Hedger, 2007).…”