title: Candida albicans delays HIV-1 replication in macrophages.
abstract: Macrophages are one of the most important HIV-1 target cells. Unlike CD4(+) T cells, macrophages are resistant to the cytophatic effect of HIV-1. They are able to produce and harbor the virus for long periods acting as a viral reservoir. Candida albicans (CA) is a commensal fungus that colonizes the portals of HIV-1 entry, such as the vagina and the rectum, and becomes an aggressive pathogen in AIDS patients. In this study, we analyzed the ability of CA to modulate the course of HIV-1 infection in human monocyte-derived macrophages. We found that CA abrogated HIV-1 replication in macrophages when it was evaluated 7 days after virus inoculation. A similar inhibitory effect was observed in monocyte-derived dendritic cells. The analysis of the mechanisms responsible for the inhibition of HIV-1 production in macrophages revealed that CA efficiently sequesters HIV-1 particles avoiding its infectivity. Moreover, by acting on macrophages themselves, CA diminishes their permissibility to HIV-1 infection by reducing the expression of CD4, enhancing the production of the CCR5-interacting chemokines CCL3/MIP-1α, CCL4/MIP-1β, and CCL5/RANTES, and stimulating the production of interferon-α and the restriction factors APOBEC3G, APOBEC3F, and tetherin. Interestingly, abrogation of HIV-1 replication was overcome when the infection of macrophages was evaluated 2-3 weeks after virus inoculation. However, this reactivation of HIV-1 infection could be silenced by CA when added periodically to HIV-1-challenged macrophages. The induction of a silent HIV-1 infection in macrophages at the periphery, where cells are continuously confronted with CA, might help HIV-1 to evade the immune response and to promote resistance to antiretroviral therapy.
authors.affiliation: Instituto de Investigaciones Médicas en Retrovirus y SIDA (INBIRS), Facultad de Medicina, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.
authors.forename: Christian
authors.initials: C
authors.lastname: Rodriguez Rodrigues
authors.forename: Federico
authors.initials: F
authors.lastname: Remes Lenicov
authors.forename: Carolina
authors.initials: C
authors.lastname: Jancic
authors.forename: Juan
authors.initials: J
authors.lastname: Sabatté
authors.forename: Mercedes
authors.initials: M
authors.lastname: Cabrini
authors.forename: Ana
authors.initials: A
authors.lastname: Ceballos
authors.forename: Antonela
authors.initials: A
authors.lastname: Merlotti
authors.forename: Heidi
authors.initials: H
authors.lastname: Gonzalez
authors.forename: Matías
authors.initials: M
authors.lastname: Ostrowski
authors.forename: Jorge
authors.initials: J
authors.lastname: Geffner
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism; D002176:Candida albicans / Q000502:physiology*; D018925:Chemokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism / Q000382:microbiology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000382:microbiology / Q000821:virology; D008024:Ligands; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology* / Q000821:virology*; D019713:Receptors, CCR5 / Q000378:metabolism; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D015704:CD4 Antigens; D018925:Chemokines; D008024:Ligands; D019713:Receptors, CCR5