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.
Highlights
Transmitted infections (STIs) are a main health issue worldwide [1], and the male genital tract is a portal of entry for numerous sexually transmitted pathogens, including viral and bacterial pathogens, such as human papilloma virus (HPV) [2], Chlamydia trachomatis [3] or Neisseria gonorrhoeae [4]
Numerous pathogens including viruses and bacteria use the human penis as a portal of entry into the body and a vaccine locally active against such pathogens is key to control the spread of STIs
Establishment of immune memory against pathogens occurs naturally after infection and permits to establish a faster specific immune response following a second contact with the pathogen
Summary
Transmitted infections (STIs) are a main health issue worldwide [1], and the male genital tract is a portal of entry for numerous sexually transmitted pathogens, including viral and bacterial pathogens, such as human papilloma virus (HPV) [2], Chlamydia trachomatis [3] or Neisseria gonorrhoeae [4]. We and others demonstrated that human immunodeficiency virus type 1 (HIV-1) targets the penile foreskin and urethra [5,6,7,8,9,10]. Initial HIV-1 vaccine studies were able to induce HIV-1 specific mucosal antibodies, non-neutralizing, in the male genital mucosa [11]. Exposed seronegative (ESN) men harbor high urethral concentrations of HIV-1-specific IgA induced by nonprotected insertive sexual intercourses with seropositive female partners [12]. These studies indicate that the human male genitals, as in other species [13], are effector sites. The lack of progress in developing vaccines to stimulate local protection in the penis is mainly due to the lack of information on the penile immune system
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
