title: Monocyte-derived IL-5 reduces TNF production by Mycobacterium tuberculosis-specific CD4 T cells during SIV/M. tuberculosis coinfection.
abstract: HIV-infected individuals are significantly more susceptible to tuberculosis (TB) than uninfected individuals. Although it is established that HIV reduces Mycobacterium tuberculosis-specific T cell responses, the causes of this dysfunction are not known. We used the cynomolgus macaque model of TB to demonstrate that ex vivo SIV reduces the frequency of M. tuberculosis-specific TNF and IFN-γ-producing T cells within 24 h after infection. In vivo, T cell IFN-γ responses in granulomas from animals with SIV/M. tuberculosis coinfection were lower than SIV-negative animals with active TB. The SIV effects on the inhibition of T cell responses were primarily on APCs and not the T cells directly. Specifically, reductions in the frequency of TNF-producing M. tuberculosis-specific CD4 T cells were caused, at least in part, by SIV-induced production of monocyte derived IL-5.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Collin R
authors.initials: CR
authors.lastname: Diedrich
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Mattila
authors.forename: JoAnne L
authors.initials: JL
authors.lastname: Flynn
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D015848:Interleukin-5 / Q000276:immunology / Q000378:metabolism*; D008252:Macaca fascicularis; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000276:immunology; D014376:Tuberculosis / Q000150:complications* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha