The Human Penis Is a Genuine Immunological Effector Site

Abstract

The human penis is a main portal of entry for numerous pathogens, and vaccines able to control resulting infections locally are highly desirable. However, in contrast to the gastrointestinal or vaginal mucosa, the penile immune system and mechanisms inducing a penile immune response remain elusive. In this descriptive study, using multiparametric flow cytometry and immunohistochemistry, we characterized mucosal immune cells such as B, T, and natural killer (NK) cells from the urethra, fossa, and glans of human adult penile tissues. We show that memory B lymphocytes and CD138+ plasma cells are detected in all penile compartments. CD4+ and CD8+ T lymphocytes reside in the epithelium and lamina propria of the penile regions and have mostly a resting memory phenotype. All penile regions contain CD56dim NK cells surface expressing the natural cytotoxicity receptor NKp44 and the antibody-dependent cell cytotoxicity receptor CD16. These cells are also able to spontaneously secrete pro- and anti-inflammatory cytokines, such as IL-17 and IL-22. Finally, CCR10 is the main homing receptor detected in these penile cells although, together with CCR3, CCR6, and CCR9, their expression level differs between penile compartments. Unlike antigen-presenting cells which type differ between penile regions as we reported earlier, urethral, fossa, and glans content in immune B, T, and NK cells is comparable. However, median values per each analysis suggest that the glans, containing higher number and more activated NK cells together with higher number of terminally differentiate effector CD8+ T cells, is a superior effector site than the urethra and the fossa. Thus, the human penis is an immunologically active tissue containing the cellular machinery required to induce and produce a specific and effective response against mucosal pathogens. It can therefore be considered as a classic mucosal effector site, a feature that must be taken into account for the elaboration of efficient strategies, including vaccines, against sexually transmitted infections.

From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract

“…The lamina propria of the foreskin encompasses predominantly macrophages, as well as memory CD8+ and a few CD4+ T lymphocytes including T helper 17 cells (19,320,555). The lamina propria of the penile urethra contains numerous T lymphocytes, essentially memory CD8+ T cells with a few CD4+ naïve and memory T cells (most CD103+), natural killer (NK), memory B, and IgA and IgM producing plasma cells, but only a few macrophages (19,618). In addition to the urethra, memory B cells and IgA and J chain + plasma cells are found in the glans and fossa navicularis mucosa, but are rare in the meatus (19,505,618).…”

“…The lamina propria of the penile urethra contains numerous T lymphocytes, essentially memory CD8+ T cells with a few CD4+ naïve and memory T cells (most CD103+), natural killer (NK), memory B, and IgA and IgM producing plasma cells, but only a few macrophages (19,618). In addition to the urethra, memory B cells and IgA and J chain + plasma cells are found in the glans and fossa navicularis mucosa, but are rare in the meatus (19,505,618). Compared to the urethra and fossa, the glans contains a higher number of NK cells that are more activated, as well as a higher number of effector CD8+ cells (618).…”

“…The penis is a major portal of entry for many pathogens and an immunologically active site. The immunity of the penis has been reviewed in detail elsewhere (558,618) and only a few relevant key aspects are presented here. While the urethra displays classic mucosal effector features, the glans has even more activated natural killer (NK) cells and terminallydifferentiated effector CD8+ T cells (618).…”

“…The immunity of the penis has been reviewed in detail elsewhere (558,618) and only a few relevant key aspects are presented here. While the urethra displays classic mucosal effector features, the glans has even more activated natural killer (NK) cells and terminallydifferentiated effector CD8+ T cells (618). The penile urethra contains numerous polymeric immunoglobulin A (IgA) and IgM producing plasma cells (558).…”

Impact of Endemic Infections on HIV Susceptibility in Sub-Saharan Africa

“…Among heterosexual men, the penis is the key organ at which virtually all HIV infections are acquired. Throughout the penile tissue, abundant macrophages and Langerhans cells comprise the main antigen presenting cells and together with plasma and T cells mediate adaptive immune responses [45–52]. In heterosexual men, circumcision reduces HIV incidence by 50-60% [22–24], suggesting that the foreskin is an important site of HIV acquisition, although other penile tissues such as the urethra may also play a role in HIV acquisition [53, 54].…”