Host Immunity to Mycobacterium tuberculosis Infection Is Similar in Simian Immunodeficiency Virus (SIV)-Infected, Antiretroviral Therapy-Treated and SIV-Naïve Juvenile Macaques.

Autor:	Larson EC; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Ellis AL; Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, Wisconsin, USA., Rodgers MA; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Gubernat AK; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Gleim JL; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Moriarty RV; Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, Wisconsin, USA., Balgeman AJ; Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, Wisconsin, USA., Menezes YK; Department of Immunobiology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil., Ameel CL; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Fillmore DJ; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Pergalske SM; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Juno JA; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia., Maiello P; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., White AG; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Borish HJ; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Godfrey DI; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia., Kent SJ; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.; Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Centre Clinical School, Monash University, Melbourne, Victoria, Australia., Ndhlovu LC; Department of Medicine, Division of Infectious Disease, Weill Cornell Medicine, New York, New York, USA., O'Connor SL; Department of Pathology and Laboratory Medicine, University of Wisconsin - Madison, Wisconsin, USA.; Wisconsin National Primate Research Center, University of Wisconsin - Madison, Wisconsin, USA., Scanga CA; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2023 May 16; Vol. 91 (5), pp. e0055822. Date of Electronic Publication: 2023 Apr 11.
DOI:	10.1128/iai.00558-22
Abstrakt:	Pre-existing HIV infection increases tuberculosis (TB) risk in children. Antiretroviral therapy (ART) reduces, but does not abolish, this risk in children with HIV. The immunologic mechanisms involved in TB progression in both HIV-naive and HIV-infected children have not been explored. Much of our current understanding is based on human studies in adults and adult animal models. In this study, we sought to model childhood HIV/Mycobacterium tuberculosis (Mtb) coinfection in the setting of ART and characterize T cells during TB progression. Macaques equivalent to 4 to 8 year-old children were intravenously infected with SIVmac239M, treated with ART 3 months later, and coinfected with Mtb 3 months after initiating ART. SIV-naive macaques were similarly infected with Mtb alone. TB pathology and total Mtb burden did not differ between SIV-infected, ART-treated and SIV-naive macaques, although lung Mtb burden was lower in SIV-infected, ART-treated macaques. No major differences in frequencies of CD4 + and CD8 + T cells and unconventional T cell subsets (Vγ9+ γδ T cells, MAIT cells, and NKT cells) in airways were observed between SIV-infected, ART-treated and SIV-naive macaques over the course of Mtb infection, with the exception of CCR5+ CD4 + and CD8 + T cells which were slightly lower. CD4 + and CD8 + T cell frequencies did not differ in the lung granulomas. Immune checkpoint marker levels were similar, although ki-67 levels in CD8 + T cells were elevated. Thus, ART treatment of juvenile macaques, 3 months after SIV infection, resulted in similar progression of Mtb and T cell responses compared to Mtb in SIV-naive macaques. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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