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Background: Dendritic cells (DC) contribute to initiate and maintain the host defense against pathogens. In viremic HIV⁺ adults, myeloid DC (MDC) and plasmacytoid DC (PDC) are depleted, resulting in impaired IFN-a and IL-12 production.

Methods: We evaluated MDC and PDC subsets in a cross-sectional cohort of 39 HIV-1⁺ children (age: 11±4.3, 36 on HAART) and 14 age-matched HIV-1^- children. Percentage of CD4 (<20% = 6; 20 to 30% = 15; >30% = 18), viral load (<400 = 21; 400 to 50,000 = 12; >50,000 = 6) or 1994 CDC classification (N = 6, A = 7, B = 7, C = 19) were used in analysis. Mann-Whitney’s U test, Kruskal-Wallis’ ANOVA and Spearman correlations tests were applied.

Results: We observed a strong positive correlation between levels of serum HIV RNA and % CD4, both of which were also correlated with d copies/mL. LPA responses to C. albicans, indicating a functional recovery of adaptive immune responses upon viral suppression in our cohort.

In contrast to observations in adults, whole blood immunofluorescence analysis of Lin-1^-/HLA-DR⁺/CD11c⁺ MDC and Lin-1^-/HLA-DR⁺/CD123⁺ PDC revealed frequencies of MDC and PDC that were not significantly different between HIV⁺ and control children. No significant difference was observed between % CD4, HIV RNA or CDC classification-based subsets. Expression of the maturation markers CD86 and of CD95 was also similar between uninfected and infected children. However, CD4 counts and HIV RNA showed significant positive and negative correlations, respectively, with PDC frequencies, suggesting an impact of these variables on PDC frequencies as a result of immune reconstitution. Functional correlates of PDC subsets, i.e. Influenza virus PR8 and/or CpG-2216-mediated IFN-a production, showed significantly lower levels in HIV⁺ children; this difference was maintained in all subgroups. In addition, no correlation was found between PDC frequency and IFN-a production, supporting the hypothesis that lack of IFN-a secretion by circulating PDC results form functional impairment, which is not reversed by viral suppression and immune reconstitution. LPS-induced IL-12 production in PBMC from any subset of HIV⁺ children was not significantly different from uninfected controls, supporting the specificity of the impairment of the PDC subset.

Conclusions: In contrast to adults, HIV infection in children impairs PDC function, but not their frequency, irrespective of viral load, indicating a persistent impairment of the Innate Immune system.

Keywords: Dendritic cell; innate immunity; pediatric