Semen prostaglandins drive dendritic cell differentiation towards a non-inflammatory profile

F. REMES LENICOV; C. RODRIGUEZ RODRIGUES; M. CABRINI; J. SABATTÉ; M. OSTROWSKI; M. DONALDSON; R.A. PASQUALINI; J. GEFFNER; A. CEBALLOS

Buenos Aires

Simposio; 3rd Latin American Symposium in Reproductive Immunology; 2011

Latin American Society of Reproductive Immunology

Introduction. Semen immunomodulatory properties are well recognized, but details are lacking regarding its effect on dendritic cells, the immune cells in charge of deciding the type of response against foreign antigens. This study analyzes the ability of spermatozoa and seminal plasma to modulate the differentiation profile of dendritic cells (DC).   Methods. Semen samples from  healthy donors were used to obtain seminal plasma and spermatozoa (purified by density gradient centrifugation). DC were obtained from monocytes cultured with GM-CSF and IL-4 for 5 days, in the absence or presence of spermatozoa (spermatozoa: monocyte ratio 4:1) or seminal plasma (1:5000 dilution). DC phenotype was analyzed by flow cytometry and their ability to induce proliferation of allogeneic lymphocytes was assessed using CFSE-labeled lymphocytes.   Results. Monocytes cultured in the presence of spermatozoa or seminal plasma resulted in DC characterized by reduced expression of CD1a and increased expression of CD14. The mean fluorescence intensity (MFI) for CD1a was: 7464±106, 766±35 and 210±25 (controls vs spermatozoa- or seminal plasma-treated cells, respectively; p<0.05). These CD1a-CD14+ cells showed increased production of IL-10 but not IL-12p70. In addition, DC differentiated in the presence of spermatozoa showed a lower ability to induce the proliferation of alloreactive lymphocytes (p<0.05), and a higher ability to induce the expansion of CD25+FOXP3+ cells: % of CD25+FOXP3+ cells: 5±1 vs 12±4 (p<0.05 control vs spermatozoa-treated DC). Importantly, prostaglandin receptor antagonists inhibited the generation of CD1a-CD14+ cells.   Conclusion. Exposure to semen prostaglandins skews dendritic cell differentiation towards a non-inflamatory profile, thus protecting sperm from an immune attack.