<i>Mycobacterium bovis</i>BCG-Specific Th17 Cells Confer Partial Protection against<i>Mycobacterium tuberculosis</i>Infection in the Absence of Gamma Interferon

Wozniak, Teresa M.; Saunders, Bernadette M.; Ryan, Anthony A.; Britton, Warwick J.

doi:10.1128/iai.01392-09

Cited by 118 publications

(100 citation statements)

References 29 publications

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“…Antigen-specific CD4 1 T-cell responses are important in defense against common respiratory pathogens including Mtb (22)(23)(24) and influenza virus (25). Consistent with our previous observations (5) and those of others (4), we found low frequencies of total mycobacteria-and influenza-specific cytokine-producing Th1 CD4 1 T cells in BAL but not peripheral blood in asymptomatic HIV-infected adults.…”

Section: Discussionsupporting

confidence: 81%

“…Specifically, the proportion of mycobacteria-and influenzaspecific IFN 1 TNF 1 DP CD4 1 T cells were lower than those observed in HIVuninfected adults. IFN-g and TNF play important roles in defense against Mtb (1,9,22) and influenza virus infections (26,27). Our findings suggest preferential depletion of these antigen-specific polyfunctional CD4 1 T cells by HIV and incomplete recovery during long-term ART.…”

Section: Discussionmentioning

confidence: 68%

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Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4⁺T-Cell Responses to Mycobacteria

Jambo

Banda

Afran

et al. 2014

Am J Respir Crit Care Med

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Rationale: HIV-infected persons on antiretroviral therapy (ART) remain at higher risk of pulmonary tuberculosis (TB) than HIV-uninfected individuals. This increased susceptibility may be caused by impairment of alveolar macrophage (AM) function and/or mycobacteria-specific alveolar CD4 1 T-cell responses observed in HIV-infected ART-naive adults.Objectives: To determine whether ART was associated with improvement in both AM function, assessed by phagosomal proteolysis, and alveolar CD4 1 T-cell responses to Mycobacterium in HIV-infected individuals.Methods: Peripheral blood was drawn and bronchoalveolar lavage (BAL) performed on healthy, 35 HIV-uninfected, 25 HIV-infected ART-naive, and 50 HIV-infected ART-treated asymptomatic adults. Phagosomal proteolysis of AM was assessed with fluorogenic beads. Mycobacteria-specific CD4 1 T-cell responses were measured by intracellular cytokine staining.Measurements and Main Results: HIV-infected adults on ART exhibited lower plasma HIV viral load and higher blood CD4 1 T-cell count than ART-naive adults. AM proteolysis and total mycobacteria-specific Th1 CD4 1 T-cell responses in individuals on ART for greater than or equal to 4 years were similar to HIVuninfected control subjects but those on ART for less than 4 years had impaired responses. Total influenza-specific alveolar Th1 CD4 1 Tcell responses were intact in all individuals receiving ART. In contrast, BAL and blood mycobacteria-specific polyfunctional CD4 1 T-cell responses were impaired in adults on ART irrespective of duration.Conclusions: AM and mycobacteria-specific alveolar CD4 1 T-cell responses in HIV-infected adults on ART for less than 4 years are impaired and may partly explain the high risk of TB in HIV-infected individuals on ART. Strategies to augment ART to improve lung immune cell function and reduce the high incidence of TB in HIVinfected adults who initiate ART should be investigated.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 68%

Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4⁺T-Cell Responses to Mycobacteria

Jambo

Banda

Afran

et al. 2014

Am J Respir Crit Care Med

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“…IL-17 has been shown to confer protection against Mtb in murine model. 42 This is partially independent of IFN-g and appears to be associated with IL-17-driven granuloma formation. 42,43 Immune protection in Mtb infection is certainly multifaceted; for example, we show here that IL-7 decreased in NHP PBMCs IL-10 and Foxp3 gene expression, whereas only IL-7, yet not IFN-g yielded increased IL-17 gene and protein expression in PBMCs from 5/5 NHPs (Figure 2).…”

Section: Il-mentioning

confidence: 99%

“…42 This is partially independent of IFN-g and appears to be associated with IL-17-driven granuloma formation. 42,43 Immune protection in Mtb infection is certainly multifaceted; for example, we show here that IL-7 decreased in NHP PBMCs IL-10 and Foxp3 gene expression, whereas only IL-7, yet not IFN-g yielded increased IL-17 gene and protein expression in PBMCs from 5/5 NHPs (Figure 2). Thus, increased IL-17 protein detection in situ and IL-7-driven IL-17 production in vitro suggest that the 6 exonspanning IL-7 protein mediates beneficial effects in Mtb infection via IL-17 induction.…”

Section: Il-mentioning

confidence: 99%

Increased (6 exon) interleukin-7 production after M. tuberculosis infection and soluble interleukin-7 receptor expression in lung tissue

et al. 2011

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Interleukin-7 (IL-7) and the IL-7 receptor (IL-7R) have been shown to be alternatively spliced in infectious diseases. We tested IL-7 and IL-7R splicing in a tuberculosis (TB)-vaccine/Mycobacterium tuberculosis (Mtb)-challenge model in non-human primates (NHPs). Differential IL-7 splicing was detected in peripheral blood mononuclear cells (PBMCs) from 15/15 NHPs showing 6 different IL-7 spliced isoforms. This pattern did not change after infection with virulent Mtb. We demonstrated increased IL-7 (6 exon) and IL-17 protein production in lung tissue along with concomitant decreased transforming growth factor-b (TGF-b) from NHPs (vaccinated with a recombinant BCG (rBCG)) who showed increased survival after Mtb challenge. IL-7 increased IL-17 and interferon-g (IFN-g) gene and protein expression in PBMCs. Mtb-infected NHPs showed differential IL-7R splicing associated with the anatomical location and tissue origin, that is, in lung tissue, hilus, axillary lymph nodes (LNs) and spleen. Differential splicing of the IL-7R was typical for healthy (non-Mtb infected) and for Mtb-infected lung tissue with a dominant expression of soluble IL-7R (sIL-7R) receptor lacking exon 6 (9:1 ratio of sIL-7R/cell-bound IL-7R). Differential ratios of cell-bound vs sIL-7R could be observed in hilus and axillary LNs from Mtb-infected NHPs with an inversed ratio of 1:9 (sIL-7R/cell-bound IL-7R) in spleen and PBMCs. Soluble IL-7R is exclusively present in lung tissue.

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“…Therefore, diagnosis of an acute infection can be made by noting the presence of the antigen-specific effector T cells in a patient's blood or serum sample and by measuring the release of cytokines by the T effector cells when re-exposed to antigen in vitro. It has been shown recently that TB-specific Th1, Th22, and Th17 cells have an essential role in the immunity against TB infection; this provides a potential target for diagnosis and therapeutic intervention in TB disease (Qiao et al, 2011;Wozniak et al, 2010).…”

Section: Interferon-gamma Release Assays (Igras)mentioning

confidence: 99%

Diagnosis of Mycobacterium tuberculosis

Al-Zamel¹

2012

Understanding Tuberculosis - Global Experiences and Innovative Approaches to the Diagnosis

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Mycobacterium bovisBCG-Specific Th17 Cells Confer Partial Protection againstMycobacterium tuberculosisInfection in the Absence of Gamma Interferon

Cited by 118 publications

References 29 publications

Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4⁺T-Cell Responses to Mycobacteria

Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4⁺T-Cell Responses to Mycobacteria

Increased (6 exon) interleukin-7 production after M. tuberculosis infection and soluble interleukin-7 receptor expression in lung tissue

Diagnosis of Mycobacterium tuberculosis

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Mycobacterium bovisBCG-Specific Th17 Cells Confer Partial Protection againstMycobacterium tuberculosisInfection in the Absence of Gamma Interferon

Cited by 118 publications

References 29 publications

Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4+T-Cell Responses to Mycobacteria

Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4+T-Cell Responses to Mycobacteria

Increased (6 exon) interleukin-7 production after M. tuberculosis infection and soluble interleukin-7 receptor expression in lung tissue

Diagnosis of Mycobacterium tuberculosis

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Product

Resources

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Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4⁺T-Cell Responses to Mycobacteria

Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4⁺T-Cell Responses to Mycobacteria