title: Nonpathogenic SIV and Pathogenic HIV Infections Associate with Disparate Innate Cytokine Signatures in Response to Mycobacterium bovis BCG.
abstract: Infections with mycobacteria, including Mycobacterium tuberculosis (Mtb) and Mycobacterium bovis (M. bovis) BCG, are a leading cause of morbidity and mortality for HIV-infected persons. In contrast to HIV, nonpathogenic SIV infections of sooty mangabeys are characterized by a lack of clinical disease including an absence of opportunistic infections. The goal of this study was to identify innate immune responses to M. bovis BCG maintained during nonpathogenic lentiviral infections through a comparison of functional responses during pathogenic HIV or nonpathogenic SIV infections. Monocytes were evaluated for their ability to express key anti-mycobacterial cytokines TNF-α and IL-12 following a six-hour ex vivo BCG exposure. While HIV-infection was associated with a decreased percentage of IL-12-producing monocytes, nonpathogenic SIV-infection was associated with an increased percentage of monocytes producing both cytokines. Gene expression analysis of PBMC following ex vivo BCG exposure identified differential expression of NK cell-related genes and several cytokines, including IFN-γ and IL-23, between HIV-infected and control subjects. In contrast, SIV-infected and uninfected-control mangabeys exhibited no significant differences in gene expression after BCG exposure. Finally, differential gene expression patterns were identified between species, with mangabeys exhibiting lower IL-6 and higher IL-17 in response to BCG when compared to humans. Overall, this comparison of immune responses to M. bovis BCG identified unique immune signatures (involving cytokines IL-12, TNF-α, IL-23, IL-17, and IL-6) that are altered during HIV, but maintained or increased during nonpathogenic SIV infections. These unique cytokine and transcriptome signatures provide insight into the differential immune responses to Mycobacteria during pathogenic HIV-infection that may be associated with an increased incidence of mycobacterial co-infections.
authors: University of Washington Pathobiology Graduate Program, Seattle, Washington, United States of America.|Center for Infectious Disease Research, formerly Seattle Biomedical Research Institute, Seattle, Washington, United States of America.
authors: Melanie A
authors: MA
authors: Gasper
authors: Center for Infectious Disease Research, formerly Seattle Biomedical Research Institute, Seattle, Washington, United States of America.
authors: Shameek P
authors: SP
authors: Biswas
authors: Center for Infectious Disease Research, formerly Seattle Biomedical Research Institute, Seattle, Washington, United States of America.
authors: Bridget S
authors: BS
authors: Fisher
authors: Yerkes National Primate Research Center, Atlanta, Georgia, United States of America.
authors: Stephanie C
authors: SC
authors: Ehnert
authors: Center for Infectious Disease Research, formerly Seattle Biomedical Research Institute, Seattle, Washington, United States of America.
authors: David R
authors: DR
authors: Sherman
authors: Center for Infectious Disease Research, formerly Seattle Biomedical Research Institute, Seattle, Washington, United States of America.
authors: Donald L
authors: DL
authors: Sodora
mesh_terms: D000818:Animals; D016664:Cercocebus / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D007113:Immunity, Innate; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009163:Mycobacterium bovis / Q000502:physiology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D013045:Species Specificity
chemical_list: D016207:Cytokines