Semen promotes the differentiation of tolerogenic dendritic cells

F. REMES LENICOV; C. RODRIGUEZ RODRIGUES; J. SABATTÉ; M. CABRINI; C. JANCIC; M. OSTROWSKI; A. MERLOTTI; H. GONZÁLEZ; A. ALONSO; R.A. PASQUALINI; C. DAVIO; J. GEFFNER; A. CEBALLOS

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Lugar: Bethesda; Año: 2012 p. 4777 - 4786

0022-1767

Seminal plasma is not just a carrier for spermatozoa. It contains high concentrations ofcytokines, chemokines, and other biological compounds which are able to exert potenteffects on the immune system of the receptive partner. Previous studies have shown thatsemen induces an acute inflammatory response at the female genital mucosa aftercoitus. Moreover, it induces regulatory mechanisms that allow the fetus (a semiallograft)to grow and develop in the uterus. The mechanisms underlying theseregulatory mechanisms, however, are poorly understood. In this study we show thatseminal plasma redirects the differentiation of human dendritic cells towards aregulatory profile. Dendritic cells differentiated from human monocytes in the presenceof high dilutions of seminal plasma did not express CD1a, but showed high levels ofCD14. They were unable to develop a fully mature phenotype in response to LPS, TNF-α, CD40L, Pam2CSK4 (TLR2/6 agonist) or Pam3CSK4 (TLR1/2 agonist). Uponactivation, they produced low amounts of the inflammatory cytokines IL-12p70, IL-1β,TNF-α, and IL-6, but expressed a high ability to produce IL-10 and TGF-β. Inhibitionof the prostaglandin receptors EP2 and EP4 prevented the tolerogenic effect induced byseminal plasma on the phenotype and function of dendritic cells, suggesting that Eseriesprostaglandins play a major role. By promoting a tolerogenic profile in dendriticcells, seminal plasma might favor fertility, but might also compromise the capacity ofthe receptive partner to mount an effective immune response against sexuallytransmitted pathogens.