title: Candida albicans-induced DC activation partially restricts HIV amplification in DCs and increases DC to T-cell spread of HIV.
abstract: 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.
authors.affiliation: Center for Biomedical Research, Population Council, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Vachot
authors.forename: Vennansha G
authors.initials: VG
authors.lastname: Williams
authors.forename: Julian W
authors.initials: JW
authors.lastname: Bess
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Melissa
authors.initials: M
authors.lastname: Robbiani
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D002176:Candida albicans; D002177:Candidiasis / Q000150:complications / Q000276:immunology*; D002452:Cell Count; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006678:HIV; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000821:virology; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051858:Forkhead Transcription Factors; D007136:Immunoglobulins; D016753:Interleukin-10; D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen; C418974:FOXP3 protein, human