Dendritic Cells Derived from Hemozoin-Loaded Monocytes Display a Partial Maturation Phenotype that Promotes HIV-1 Trans-Infection of CD4+ T Cells and Virus Replication

Abstract

Coinfection of HIV-1 patients with Plasmodium falciparum, the etiological agent of malaria, results in a raise of viral load and an acceleration of disease progression. The primary objective of this study was to investigate whether the malarial pigment hemozoin (HZ), a heme by-product of hemoglobin digestion by malaria parasites, can affect HIV-1 transmission by monocytes-derived dendritic cells (DCs) to CD4+ T cells when HZ is initially internalized in monocytes before their differentiation in DCs. We demonstrate in this study that HZ treatment during the differentiation process induces an intermediate maturation phenotype when compared with immature and fully mature DCs. Furthermore, the DC-mediated transfer of HIV-1 is enhanced in presence of HZ, a phenomenon that may be linked with the capacity of HZ-loaded cells to interact and activate CD4+ T cells. Altogether our findings suggest a new mechanism that could partially explain the increased HIV-1 virus production during a coinfection with P. falciparum. Understanding the multifaceted interactions between P. falciparum and HIV-1 is an important challenge that could lead to the development of new treatment strategies.

HIV-1TransInfection of CD4+T Cells by Professional Antigen Presenting Cells

“…The enhancing effect of malaria on DC-mediated trans infection could be due to hemozoin, a pigment that is released in excess after destruction of the infected erythrocytes. The hemozoin-loaded DC are partially activated, leading to increased activation and trans infection of CD4 + T cells [285, 286]. …”

The Impact of HIV Coinfection on Cerebral Malaria Pathogenesis

“…These semi-mature dendritic cells have a lower surface expression of CCR5 than immature dendritic cells and are less permissive to virus infection. However, these cells exhibit an enhanced transfer of HIV-1 to CD4+ T cells and HIV-1 replication in CD4+ T cells is promoted by contact with these semi-mature, Hz-containing dendritic cells [43]. There does not appear to be a direct effect of Hz on CD4+ T cells [42].…”

A look at HIV journey

“…Maturation of dendritic cells can readily occur upon most microbial invasion and thus could be a means of increased HIV dissemination in lymphoid tissues during pathogenic co-infection. Recent reports showed that the malarial pigment hemozoin can partially mature DC [22] and activate CD4 þ T cells, leading to a significant enhancement of dendritic cell-mediated transfer of HIV-1 infection [23]. With previous reports, this is another cumulative evidence of the nefarious effect of pathogen co-infection on dendritic cell subversion and HIV spread.…”