Immune characterization of the HBHA-specific response in mycobacterium tuberculosis-infected patients with or without HIV infection

Giovanni Delogu, Flavio De Maio, Carmela Pinnetti, Teresa Chiacchio, Valentina Vanini, Gilda Cuzzi, Alessandro Sampaolesi, Andrea Antinori, Delia Goletti

Risultato della ricerca: Contributo in rivistaArticolo in rivista

19 Citazioni (Scopus)

Abstract

Introduction RD1-based Interferon-γ Release Assays (IGRAs) cannot distinguish latent from active tuberculosis (TB) disease. Conversely, a positive response to heparin-binding haemagglutinin (HBHA)-based IGRAs, among TB-infected subjects, correlates with Mycobacterium tuberculosis (Mtb) containment and low risk of TB progression. The aim of this study was to characterize HBHA-immune responses in HIV-infected and uninfected subjects with active TB or latent TB infection (LTBI). Methods 49 subjects were prospectively enrolled: 22 HIV-uninfected (13 TB, 9 LTBI) and 27 HIV-infected (12 HIV-TB, 15 HIV-LTBI). Whole blood and peripheral blood mononuclear cells were stimulated with HBHA and RD1 antigens. Interferon (IFN)γ release was evaluated by ELISA whereas cytokine profile [IFNγ, tumor necrosis (TNF)α, interleukin (IL)2] and phenotype (CD45RA, CCR7) by flow cytometry. Results Among LTBI individuals, HBHA stimulation induced IFNγ release in all the HIV-uninfected, while, only 4/15 HIV-infected responded. Within the active TB, only 5/13 HIV-uninfected and 1/12 HIV-TB patients responded. Interestingly, by cytometry we showed that CD4+T-cells response to HBHA was significantly impaired in the HIV-infected subjects with TB or LTBI compared to the HIV-uninfected subjects. The phenotype of HBHA-specific CD4 T-cells showed a predominantly central memory (CM) and effector memory (EM) phenotype without differences among the groups. Differently, HBHA-specific CD8+T-cells, showed mainly a CM and naïve phenotype in LTBI group while TB, HIV-LTBI and HIV-TB groups were characterized by EM or terminally differentiated phenotypes. Interestingly, differently than what observed for RD1, the cytokine profile of HBHA-specific T-cells evaluated by cytometry showed that the CD4+T-cells were mostly monofunctional. Conversely, CD8-specific T-cells were mostly monofunctional for both HBHA and RD1 stimulations. Conclusions These results characterize the impact of HIV infection in CD4- and CD8-specific response to HBHA in both LTBI and TB patients. HIV infection impairs the CD4 response to HBHA and likely this may lead to an impairment of TB control.
Lingua originaleEnglish
pagine (da-a)1-18
Numero di pagine18
RivistaPLoS One
Volume12
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • Adult
  • Agricultural and Biological Sciences (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cytokines
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • HIV Infections
  • Humans
  • Interferon-gamma
  • Lectins
  • Male
  • Middle Aged
  • Prospective Studies
  • Tuberculosis

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