INVESTIGADORES
REMES LENICOV Federico
congresos y reuniones científicas
Título:
Semen modulates the differentiation of monocyte-derided dendritic cells towards a tolerogenic phenotype
Autor/es:
F. REMES LENICOV; C. RODRIGUEZ RODRIGUES; C. JANCIC; J. SABATTÉ; M. CABRINI; M. DONALDSON; R.A. PASQUALINI; J. GEFFNER; A. CEBALLOS
Lugar:
Boston
Reunión:
Congreso; AIDS Vaccine 2012 Conference; 2012
Institución organizadora:
Global HIV Vaccine Enterprise
Resumen:
HIV vaccines have not been able to
provide immune protection against sexually transmitted HIV. We hypothesized
that semen has an active role in the transmission of HIV by influencing the
early events of the immune response. This study analyzed the ability of spermatozoa
and seminal plasma (SP) to modulate in vitro the differentiation profile of
human monocyte-derived dendritic cells (DC).
Spermatozoa were purified by swim-up of
semen samples from healthy donors, while SP was obtained by semen centrifugation.
DC were obtained by incubating peripheral blood monocytes (>85% purity) with
GM-CSF and IL-4 for 5 days, in the absence or presence of spermatozoa (Sp:
monocyte ratio 4:1) or SP (dilution 1:5000). DC phenotype was analyzed by flow
cytometry while cytokine production was measured by ELISA.
Differentiation of DC performed in
the presence of spermatozoa or SP resulted in a marked reduction of CD1a expreession
together with increased expression of CD14. The mean fluorescence intensity for
CD1a was: 7464 ± 106, 210 ± 25 and 766 ± 35 (p<0.05 for controls vs spermatozoa-
or SP-treated cells, respectively). We also found that spermatozoa and SP significantly
(p < 0.05) increased expression of HLA-DR, CD86 and CD80. However, stimulation
of treated DCs with LPS resulted in reduced production of IL-12p70 or IL-23,
but increased secretion of IL-10 (p < 0.01). Moreover, DC differentiated in
the presence of SP or spermatozoa induced the expansion of CD25+FOXP3+ T
lymphocytes: 5±1% vs 12 ±4% and 9 ±2% CD25+FOXP3+ cells (p<0.05, control vs
SP- or spermatozoa-treated cells respectively). Finally, the effect of SP on DC
phenotype and IL-12p70 production was partially abrogated by antgonizing
prostaglandin-E2 signalling, suggesting a role of prostaglandins as mediators
of semen effects.
Our data support the notion that semen
may alter the anti-HIV immune response by inducing a tolerogenic profile in DC.