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

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 o...

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Vydáno v:	PloS one Ročník 12; číslo 8; s. e0183846
Hlavní autoři:	Chiacchio, Teresa, Delogu, Giovanni, Vanini, Valentina, Cuzzi, Gilda, De Maio, Flavio, Pinnetti, Carmela, Sampaolesi, Alessandro, Antinori, Andrea, Goletti, Delia
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 24.08.2017 Public Library of Science (PLoS)
Témata:	Adult Antigens Biology and Life Sciences Blood CCR7 protein CD4 antigen CD4-Positive T-Lymphocytes - metabolism CD45RA antigen CD8 antigen CD8-Positive T-Lymphocytes - metabolism Containment Cytokines - metabolism Cytometry Disease Progression Drug resistance Enzyme-Linked Immunosorbent Assay Epidemiology Female Flow Cytometry Health aspects Hemagglutinins Heparin HIV HIV infections HIV Infections - complications Human immunodeficiency virus Humans Immune response Immunology Infections Infectious diseases Interferon Interferon-gamma - biosynthesis Interleukins Lectins - therapeutic use Leukocytes (mononuclear) Lymphocytes T Male Medicine and Health Sciences Memory cells Middle Aged Mycobacterium tuberculosis Patients Peripheral blood mononuclear cells Prospective Studies Stimulation Tuberculosis Tuberculosis - complications Tuberculosis - drug therapy Tuberculosis - pathology Tumor necrosis factor Vaccines Italy
ISSN:	1932-6203, 1932-6203
On-line přístup:	Získat plný text
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Shrnutí:	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). 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. 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. 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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0183846