Increased alpha-defensins 1-3 production by dendritic cells in HIV-infected individuals is associated with slower disease progression.
BACKGROUND
Defensins are natural endogenous antimicrobial peptides with potent anti-HIV activity and immuno-modulatory effects. We recently demonstrated that immature dendritic cells (DC) produce alpha-defensins1-3 and that alpha-defensins1-3 modulate DC generation and maturation. Since DC-HIV interaction plays a critical role during the first steps of HIV infection, we investigated the possible impact of alpha-defensins1-3 production by DC on disease progression.


RESULTS
Monocyte-derived DC (MDDC) were analyzed comparatively in healthy controls (HC) and HIV-infected patients, including untreated "elite" and "viremic" controllers, untreated viremic non-controllers and antiretroviral-treated patients. We found that production of alpha-defensins1-3 was significantly increased in MDDC from HIV-infected patients versus HC, and this increase was mainly due to that observed in controllers, while in non-controllers the increase was not statistically significant (controllers vs. HC, p<0.005; controllers vs. non-controllers p<0.05). Secreted alpha-defensins1-3 by immature MDDC positively correlated with CD4 T cell counts in controllers, but not in non-controllers. Moreover, independently of their clinical classification, HIV-infected patients with higher alpha-defensins1-3 secretion by immature MDDC showed slower disease progression, measured as no decrease in the number of CD4+ T-cells below 350 cell/mm(3), lower increase of plasma viral load and no initiation of treatment over time. Plasma alpha-defensins1-3 levels lacked any relationship with immunologic and virologic parameters.


CONCLUSIONS
High production of alpha-defensins1-3 by immature DCs appears as a host protective factor against progression of HIV-1 infection, suggesting potential diagnostic, therapeutic and preventive implications. This protective effect may arise from the activity of alpha-defensins1-3 to damage the virions prior and/or after their internalization by immature DC, and hence favoring a more efficient viral processing and presentation to HIV-specific CD4+ T cells, without or with a minor rate of transmission of infectious HIV-1 virions.
Rodríguez-García
Marta
M
Service of Immunology, Hospital Clínic de Barcelona, Barcelona, Spain.
Climent
Núria
N
Oliva
Harold
H
Casanova
Víctor
V
Franco
Rafael
R
Leon
Agathe
A
Gatell
José M
JM
García
Felipe
F
Gallart
Teresa
T
D000328:Adult; D018791:CD4 Lymphocyte Count; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023084:alpha-Defensins / Q000097:blood / Q000235:genetics* / Q000378:metabolism
D020033:Protein Isoforms; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C406416:human neutrophil peptide 2; C406427:human neutrophil peptide 3