Antigen-specific interferon-gamma responses and innate cytokine balance in TB-IRIS

• Published in: PloS one Vol. 9; no. 11; p. e113101
• Main Authors: Goovaerts, Odin, Jennes, Wim, Massinga-Loembé, Marguerite, Ceulemans, Ann, Worodria, William, Mayanja-Kizza, Harriet, Colebunders, Robert, Kestens, Luc
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.11.2014; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; Anti-HIV Agents - immunology; Anti-HIV Agents - therapeutic use; Antigens; Antigens, Bacterial - immunology; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Antitubercular Agents - immunology; Antitubercular Agents - therapeutic use; Biology and life sciences; Blood & organ donations; CD4 antigen; CD4 Lymphocyte Count; Comparative analysis; Cytokines; Cytokines - immunology; Cytokines - metabolism; Cytomegalovirus; Cytomegalovirus Infections - complications; Cytomegalovirus Infections - immunology; Enzyme-linked immunosorbent assay; Enzyme-Linked Immunospot Assay; Epidemiology; Female; Health sciences; Highly active antiretroviral therapy; HIV; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - immunology; HIV patients; Human immunodeficiency virus; Humans; Immune reconstitution; Immune Reconstitution Inflammatory Syndrome - complications; Immune Reconstitution Inflammatory Syndrome - immunology; Immune response; Immune system; Immunologic factors; Infections; Infectious diseases; Inflammation; Influenza; Influenza, Human - complications; Influenza, Human - immunology; Innate immunity; Interferon; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin 10; Interleukin 12; Interleukin 6; Interleukin-10 - immunology; Interleukin-10 - metabolism; Interleukin-12 - immunology; Interleukin-12 - metabolism; Interleukin-6 - immunology; Interleukin-6 - metabolism; Lipopolysaccharides; Lipopolysaccharides - immunology; Male; Medicine; Medicine and Health Sciences; Mycobacterium tuberculosis - immunology; Pathogenesis; Patients; Production methods; Prospective Studies; Receptors, Interleukin-12; Sexually transmitted diseases; STD; Tuberculosis; Tuberculosis - complications; Tuberculosis - drug therapy; Tuberculosis - immunology; Tumor necrosis factor-α; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0113101

Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients receiving antiretroviral therapy (ART). TB-IRIS could be associated with an exaggerated immune response to TB-antigens. We compared the recovery of IFNγ responses to recall and TB-antigens and explored in vitro innate cytokine production in TB-IRIS patients. In a prospective cohort study of HIV-TB co-infected patients treated for TB before ART initiation, we compared 18 patients who developed TB-IRIS with 18 non-IRIS controls matched for age, sex and CD4 count. We analyzed IFNγ ELISpot responses to CMV, influenza, TB and LPS before ART and during TB-IRIS. CMV and LPS stimulated ELISpot supernatants were subsequently evaluated for production of IL-12p70, IL-6, TNFα and IL-10 by Luminex. Before ART, all responses were similar between TB-IRIS patients and non-IRIS controls. During TB-IRIS, IFNγ responses to TB and influenza antigens were comparable between TB-IRIS patients and non-IRIS controls, but responses to CMV and LPS remained significantly lower in TB-IRIS patients. Production of innate cytokines was similar between TB-IRIS patients and non-IRIS controls. However, upon LPS stimulation, IL-6/IL-10 and TNFα/IL-10 ratios were increased in TB-IRIS patients compared to non-IRIS controls. TB-IRIS patients did not display excessive IFNγ responses to TB-antigens. In contrast, the reconstitution of CMV and LPS responses was delayed in the TB-IRIS group. For LPS, this was linked with a pro-inflammatory shift in the innate cytokine balance. These data are in support of a prominent role of the innate immune system in TB-IRIS.