title: Relationship Between HIV Coinfection, Interleukin 10 Production, and Mycobacterium tuberculosis in Human Lymph Node Granulomas.
abstract: BACKGROUND
  Human immunodeficiency virus type 1 (HIV)-infected persons are more susceptible to tuberculosis than HIV-uninfected persons. Low peripheral CD4+T-cell count is not the sole cause of higher susceptibility, because HIV-infected persons with a high peripheral CD4+T-cell count and those prescribed successful antiretroviral therapy (ART) remain more prone to active tuberculosis than HIV-uninfected persons. We hypothesized that the increase in susceptibility is caused by the ability of HIV to manipulate Mycobacterium tuberculosis-associated granulomas.
  
  
  METHODS
  We examined 71 excised cervical lymph nodes (LNs) from persons with HIV and M. tuberculosis coinfection, those with HIV monoinfection, and those with M. tuberculosis monoinfection with a spectrum of peripheral CD4+T-cell counts and ART statuses. We quantified differences in M. tuberculosis levels, HIV p24 levels, cellular response, and cytokine presence within granulomas.
  
  
  RESULTS
  HIV increased M. tuberculosis numbers and reduced CD4+T-cell counts within granulomas. Peripheral CD4+T-cell depletion correlated with granulomas that contained fewer CD4+and CD8+T cells, less interferon γ, more neutrophils, more interleukin 10 (IL-10), and increased M. tuberculosis numbers. M. tuberculosis numbers correlated positively with IL-10 and interferon α levels and fewer CD4+and CD8+T cells. ART reduced IL-10 production.
  
  
  CONCLUSIONS
  Peripheral CD4+T-cell depletion correlated with increased M. tuberculosis presence, increased IL-10 production, and other phenotypic changes within granulomas, demonstrating the HIV infection progressively changes these granulomas.
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine.
authors.forename: Collin R
authors.initials: CR
authors.lastname: Diedrich
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine.
authors.forename: Jennifer
authors.initials: J
authors.lastname: O'Hern
authors.affiliation: Francis Crick Institute Mill Hill Laboratory.
authors.forename: Maximiliano G
authors.initials: MG
authors.lastname: Gutierrez
authors.affiliation: Division of Anatomical Pathology.
authors.forename: Nafiesa
authors.initials: N
authors.lastname: Allie
authors.affiliation: Division of Anatomical Pathology.
authors.forename: Patricia
authors.initials: P
authors.lastname: Papier
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine.|Department of Medicine, University of Cape Town, South Africa.
authors.forename: Graeme
authors.initials: G
authors.lastname: Meintjes
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Coussens
authors.affiliation: Division of Anatomical Pathology.|Department of Medicine, University of Cape Town, South Africa.
authors.forename: Helen
authors.initials: H
authors.lastname: Wainwright
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine.|Department of Medicine, University of Cape Town, South Africa.|Francis Crick Institute Mill Hill Laboratory.|Department of Medicine, Imperial College London, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
mesh_terms: D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000382:microbiology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000382:microbiology / Q000821:virology; D060085:Coinfection / Q000378:metabolism* / Q000382:microbiology / Q000821:virology; D005260:Female; D006099:Granuloma / Q000378:metabolism* / Q000382:microbiology / Q000821:virology; D015658:HIV Infections / Q000378:metabolism* / Q000382:microbiology / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism* / Q000382:microbiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity; D014376:Tuberculosis / Q000378:metabolism* / Q000382:microbiology / Q000821:virology; D055815:Young Adult
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: HIV; IL-10; antiretroviral therapy; coinfection; granuloma; histology; lymph node; mycobacterium; tuberculosis