Expression of CD1d and ligand-induced cytokine production are tissue-specific in mucosal epithelia of the human lower reproductive tract

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; Division of Reproductive Biology, Department of Obstetrics and Gynecology, Boston Medical Center, Boston University School of Medicine, 715 Albany Street, Evans#241, Boston, MA 02445; Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; Division of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, MA 02118; Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112

^* To whom correspondence should be addressed. Email: schustd{at}health.missouri.edu.

	Abstract

Mucosal epithelia of human lower reproductive tract (vagina, cervix, and penile urethra) are exposed to sexually transmitted microbes, including Chlamydia trachomatis. The in vivo susceptibility of each tissue to infection by Chlamydia trachomatis is quite distinct. CD1d is expressed on the surface of antigen presenting cells, including mucosal epithelial cells, and interacts specifically with invariant NKT cells. Invariant NKT cells play a role in both innate and adaptive immune responses to microbes. We here assessed CD1d expression in normal reproductive tissues using immunohistochemistry. Immortalized epithelial cell lines from the human lower reproductive tract (vagina, endocervix, and penile urethra) were examined for CD1d expression and for ligand-induced cytokine production induced by CD1d crosslinking. CD1d expression in normal tissues was strong in the vagina but weak in endocervix and penile urethra. IFN exposure induced CD1d transcription in all cells studied, with strongest induction in vaginal cells. Flow cytometry revealed that cell-surface expression of CD1d was observed in the vaginal and penile urethral epithelial cells but not endocervical cells. Ligation of surface-expressed CD1d using monoclonal antibody crosslinking promoted IL-12 and IL-15, but not IL-10, production in vaginal and penile urethral cells. No induction was demonstrated in endocervical cells. CD1d-mediated cytokine production in penile urethral cells was abrogated by Chlamydia trachomatis infection. Basal deficiency in CD1d-mediated immune responsiveness may result in susceptibility to sexually transmitted agents. Decreased CD1d-mediated signaling may help Chlamydia trachomatis evade detection by innate immune cells.