Semen promotes the differentiation of tolerogenic dendritic cells.
Seminal plasma is not just a carrier for spermatozoa. It contains high concentrations of cytokines, chemokines, and other biological compounds that are able to exert potent effects on the immune system of the receptive partner. Previous studies have shown that semen induces an acute inflammatory response at the female genital mucosa after coitus. Moreover, it induces regulatory mechanisms that allow the fetus (a semiallograft) to grow and develop in the uterus. The mechanisms underlying these regulatory mechanisms, however, are poorly understood. In this study, we show that seminal plasma redirects the differentiation of human dendritic cells (DCs) toward a regulatory profile. DCs differentiated from human monocytes in the presence of high dilutions of seminal plasma did not express CD1a but showed high levels of CD14. 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). Upon activation, 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. Inhibition of the PG receptors E-prostanoid receptors 2 and 4 prevented the tolerogenic effect induced by seminal plasma on the phenotype and function of DCs, suggesting that E-series PGs play a major role. By promoting a tolerogenic profile in DCs, seminal plasma might favor fertility, but might also compromise the capacity of the receptive partner to mount an effective immune response against sexually transmitted pathogens.
Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Universidad de Buenos Aires, Buenos Aires C1121ABG, Argentina.
Federico
F
Remes Lenicov
Christian
C
Rodriguez Rodrigues
Juan
J
Sabatté
Mercedes
M
Cabrini
Carolina
C
Jancic
Matías
M
Ostrowski
Antonela
A
Merlotti
Heidi
H
Gonzalez
Andrea
A
Alonso
Rodolfo A
RA
Pasqualini
Carlos
C
Davio
Jorge
J
Geffner
Ana
A
Ceballos
D000328:Adult; D018949:Antigens, CD1 / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000037:antagonists & inhibitors / Q000276:immunology; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000037:antagonists & inhibitors / Q000276:immunology; D012661:Semen / Q000276:immunology*
D018949:Antigens, CD1; C419393:CD1a antigen; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype