Dendritic Cells from HIV Controllers Have Low Susceptibility to HIV-1 Infection In Vitro but High Capacity to Capture HIV-1 Particles

Abstract

HIV controllers (HICs), rare HIV-1 infected individuals able to control viral replication without antiretroviral therapy, are characterized by an efficient polyfunctional and cytolytic HIV-specific CD8+ T cell response. The mechanisms underlying the induction and maintenance of such response in many HICs despite controlled viremia are not clear. Dendritic cells play a crucial role in the generation and reactivation of T cell responses but scarce information is available on those cells in HICs. We found that monocyte derived dendritic cells (MDDCs) from HICs are less permissive to HIV-1 infection than cells from healthy donors. In contrast MDDCs from HICs are particularly efficient at capturing HIV-1 particles when compared to cells from healthy donors or HIV-1 patients with suppressed viral load on antiretroviral treatment. MDDCs from HICs expressed on their surface high levels of syndecan-3, DC-SIGN and MMR, which could cooperate to facilitate HIV-1 capture. The combination of low susceptibility to HIV-1 infection but enhanced capacity to capture particles might allow MDDCs from HICs to preserve their function from the deleterious effect of infection while facilitating induction of HIV-specific CD8+ T cells by cross-presentation in a context of low viremia.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Susceptibility of MDDCs from HIC and HD to HIV-1 infection.

(A) Kinetic of HIV-1 BaL replication in MDDC from three HIC (red) and three HD (blue) in three independent and representative examples. p24 production in culture supernatants is represented as the mean ± SD of 3 independent cultures for each individual. (B) Kinetic of HIV-1 Bal production in supernatant of HIC and HD MDDC’s. p24 production in culture supernatants is represented as the mean ± IQR of 34 HD and 42 HIC. (* p<0.05; ** p<0.01; *** p<0.001) (C) Viral production at peak of infection in culture supernatants. Symbols represent the average (n = 3 independent experiments) of p24 values detected in culture supernatants for each subject (HD n = 34 and HIC n = 42). Horizontal lines represent median ± interquartile values for each group.

Fig 2. Capture of HIV-1 Bal by MDDC.

Cell-associated p24 levels 4h after exposure to virus. Symbols represent the average p24 levels (n = 3 independent experiments) for each individual (HDs n = 47, HICs n = 44 and cARTs n = 14). Horizontal lines represent median ± interquartile values for each group.

Fig 3. Antigen uptake and degradation by MDDC.

Dextran uptake (A) and ovalbumine uptake and degradation (B) by MDDC from HDs, HICs and cARTs. Top panels are examples with cells from three representative individuals of each group (light grey is the negative control, blue is one HD, red one HIC and dark grey is a cART). Bottom panels present the summary of all the experiments performed. Each circle represents one individual, and the horizontal lines represent the median ± interquartile values for each group (HD n = 31, HIC n = 23 and cART n = 16).

Fig 4. Expression of surface receptors on MDDC.

(A) Expression levels of CD4, CXCR4 and CCR5 on MDDC from HDs (n = 11), HICs (n = 12) and cARTs (n = 18). (B) Idem for DC-SIGN, MMR and Syndecan-3 (HDs n = 19, HICs n = 14 and cARTs (n = 13). Each symbol represents one individual and horizontal lines represent the median ± interquartile for each group. * represents p<0.05; ** represents p<0.01. (C) Correlations between the levels of p24 captured by MDDC and their surface expression of MMR, DC-SIGN and Syndecan-3. Each symbol represents data obtained with cells from one patients (n = 29).