Candida albicans-Induced DC Activation Partially Restricts HIV Amplification in DCs and Increases DC to T-Cell Spread of HIV

Center for Biomedical Research, Population Council, 1230 York Avenue, New York, NY 10065, USA.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 09/2008; 48(4):398-407. DOI: 10.1097/QAI.0b013e3181776bc7
Source: PubMed


Dendritic cells (DCs) are central to the innate and adaptive responses needed to control pathogens, yet HIV exploits DCs to promote infection. The influence of other pathogens on DC-HIV interplay has not been extensively studied. We used Candida albicans (Candida) as a model pathogen which elicits innate DC responses that are likely important in controlling Candida by healthy immune systems. HIV did not impede Candida-specific DC activation. Candida-induced CD80 and CD83 upregulation was greater in DCs that had captured HIV, coinciding with increased amplification in presence of T cells and reduced but persistent low-level DC infection. In contrast, HIV-infected DCs matured normally in response to Candida, but this did not shut down HIV replication in DCs, and again Candida augmented HIV amplification in DC-T-cell mixtures. HIV-infected DCs secreted more IL-10 and IL-1beta earlier than uninfected DCs and initially induced a higher frequency of CD4CD25FoxP3 T-regulatory cells in response to Candida. Elevated early IL-10 production in cocultures was evident only when azidothymidine (AZT) was included to limit T-regulatory cell infection and destruction. Therefore, HIV manipulates the DC's innate and adaptive responses to Candida to further augment HIV spread, ultimately destroying the cells needed to limit candidiasis.

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    • "Moreover, mucocutaneous candidiasis is one of the most common manifestations of HIV-1 infection [18,19]. Since CA can infect, survive and persist in macrophages [46–44,8], it is reasonable to speculate that coinfection of macrophages by HIV-1 and CA might occur in infected patients in the periphery, at the portals of HIV-1 entry. In this scenario, suppression of HIV-1 replication in macrophages induced by CA could induce opposite effects on the course of HIV-1 infection. "
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    • "We found that MDDCs could be activated by both dimorphic forms of P. marneffei for significantly promoting HIV-1 trans-infection of CD4+ T cells, and the Candida albicans (C. albicans), which has been proved to possess the similar capacity [30], was used as control. Increased expression of intercellular adhesion molecule 1 (ICAM-1) was observed on fungus-activated MDDCs, and the tighter DC-T-cell conjunction recruited significant amounts of virus particles for viral transfer. "
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