P10-13. Increased production of alpha-defensins 1–3 by dendritic cells in HIV-infected individuals is associated with a slower disease progression rate

Background

Defensins are natural peptides with potent anti-HIV activity. In humans two subfamilies exist, α- and β-defensins. α-Defensins 1–3 are mainly secreted by neutrophils, although other leukocytes also produce them. Besides their direct antimicrobial effect, α-defensins 1–3 also exert immunomodulory activities, chemoattracting leukocytes and inducing cytokines and chemokines production. We previously demonstrated that immature monocyte-derived dendritic cells (MDDC produce and secrete α-defensins 1–3 and that these defensins are able to modulate de maturation and differentiation of dendritic cells.

Methods

MDDC were generated in vitro from peripheral blood from volunteer healthy controls (HC) and HIV-infected patients, including elite controllers, viremic controllers, untreated viremic noncontrollers and treated patients. To determine α-defensins 1–3 production, culture supernatants were analyzed by ELISA and cells by real time RT-PCR for mRNA expression.

Results

Immature MDDC from HIV-infected patients secreted significantly higher levels of α-defensins 1–3 than HC (p < 0.0001). Within the HIV-infected group, this production was statistically increased in untrated HIV-infected controllers (p < 0.0001 vs HC) while in untreated viremic and treated HIV-infected patients the production was not significantly increased. The levels of α-defensins 1–3 secreted by immature MDDC positively correlated with CD4 T cell counts in the controllers group (r = 0.59; p < 0.009), but not in viremic noncontrollers and treated patients. No differences were observed in plasmatic α-defensins 1–3 levels. HIV-infected patients with higher α-defensins 1–3 secretion by immature MDDC showed a slower disease progression, measured as no decrease in the number of CD4+ T-cells below 350 cell/mm3 [HR = 8.9 (CI 1.2–65); p < 0.035], fewer increase in plasmatic viral load [HR = 2.67 (CI 1.05–6.74; p < 0.04] and no initiation of treatment [HR = 10 (CI 1.02–98.2); p < 0.05] along time.

Conclusion

Immature MDDC from HIV-infected patients who spontaneously control the infection produced higher levels of α-defensins 1–3. This increased production of alpha-defensins 1–3 was associated with a slower disease progression.