IL‐23‐dependent IL‐17 drives Th1‐cell responses following <i>Mycobacterium bovis</i> BCG vaccination

Gopal, Radha; Lin, Yinyao; Obermajer, Nataša; Slight, Samantha; Nuthalapati, Nikhil; Ahmed, Mushtaq; Kaliński, Paweł; Khader, Shabaana A.

doi:10.1002/eji.201141569

Cited by 147 publications

(159 citation statements)

References 37 publications

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“…For iNKT cells, their extremely early production of IFN-γ and/or other cytokines is thought to influence other innate immune cells and the progression of adaptive immune responses (49)(50)(51). In vitro and in vivo evidence provided here demonstrate that MAIT cells produce critical cytokines such as IFN-γ, TNF, and IL-17A in response to LVS infection-all important for initiating adaptive immunity (29,52), and controlling LVS growth (53).…”

Section: Discussionmentioning

confidence: 85%

MAIT cells are critical for optimal mucosal immune responses during in vivo pulmonary bacterial infection

Meierovics

Yankelevich

Cowley

2013

Proc. Natl. Acad. Sci. U.S.A.

321

370

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Mucosa-associated invariant T (MAIT) cells are "innate" T cells that express an invariant T-cell receptor α-chain restricted by the nonclassical MHC class I molecule MHC-related protein 1 (MR1). A recent discovery that MR1 presents vitamin B metabolites, presumably from pathogenic and/or commensal bacteria, distinguishes MAIT cells from peptide-or lipid-recognizing αβ T cells in the immune system. MAIT cells are activated by a wide variety of bacterial strains in vitro, but their role in defense against infectious assaults in vivo remains largely unknown. To investigate how MAIT cells contribute to mucosal immunity in vivo, we used a murine model of pulmonary infection by using the live vaccine strain (LVS) of Francisella tularensis. In the early acute phase of infection, MAIT cells expanded robustly in the lungs, where they preferentially accumulated after reaching their peak expansion in the late phase of infection. Throughout the course of infection, MAIT cells produced the critical cytokines IFN-γ, TNF-α, and IL-17A. Mechanistic studies showed that MAIT cells required both MR1 and IL-12 40 kDa subunit (IL-12p40) signals from infected antigen presenting cells to control F. tularensis LVS intracellular growth. Importantly, pulmonary F. tularensis LVS infection of MR1-deficient (MR1 −/− ) mice, which lack MAIT cells, revealed defects in early mucosal cytokine production, timely recruitment of IFN-γ-producing CD4 + and CD8 + T cells to the infected lungs, and control of pulmonary F. tularensis LVS growth. This study provides in vivo evidence demonstrating that MAIT cells are an important T-cell subset with activities that influence the innate and adaptive phases of mucosal immunity.tularemia | respiratory infection

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Section: Discussionmentioning

confidence: 85%

MAIT cells are critical for optimal mucosal immune responses during in vivo pulmonary bacterial infection

Meierovics

Yankelevich

Cowley

2013

Proc. Natl. Acad. Sci. U.S.A.

321

370

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“…Th17 cells accelerate the accumulation of Th1 cells and enhance Th1 antimycobacterial responses (33)(34)(35). IL-17 also plays a role in the formation and maintenance of granuloma in mycobacteria-infected lungs (36,37).…”

Section: Discussionmentioning

confidence: 99%

Role of Th1/Th17 Balance Regulated by T-bet in a Mouse Model of Mycobacterium avium Complex Disease

Matsuyama

Ishii

Yageta

et al. 2014

The Journal of Immunology

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Th1 immune responses are thought to be important in protection against intracellular pathogens. T-bet is a critical regulator for Th1 cell differentiation and Th1 cytokine production. The aim of this study was to determine the role of T-bet in host defense against Mycobacterium avium complex (MAC) infection. Wild-type mice, T-bet–deficient mice, and T-bet–overexpressing mice were infected with MAC via intratracheal inoculation. Macrophages and dendritic cells obtained from these mice were incubated with MAC. T-bet–deficient mice were highly susceptible to MAC, compared with wild-type mice and T-bet–overexpressing mice. Neutrophilic pulmonary inflammation was also enhanced in T-bet–deficient mice, but attenuated in T-bet–overexpressing mice, following MAC infection. Cytokine expression shifted toward Th1 in the lung and spleen of T-bet–overexpressing mice, but toward Th17 in T-bet–deficient mice. IFN-γ supplementation to T-bet–deficient mice reduced systemic MAC growth but did not reduce pulmonary inflammation. In contrast, neutralization of IL-17 in T-bet–deficient mice reduced pulmonary inflammation but did not affect mycobacterial growth in any organs tested. T-bet–deficient T cells tended to differentiate toward Th17 cells in vitro following exposure to MAC. Treatment with NO donor suppressed MAC-induced Th17 cell differentiation of T-bet–deficient T cells. This study identified that the fine balance between Th1 and Th17 responses is essential in defining the outcome of MAC disease. T-bet functions as a regulator for Th1/Th17 balance and is a critical determinant for host resistance to MAC infection by controlling cytokine and NO levels.

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“…1 For instance, after BCG vaccination complex cytokine profiles are induced that include elevated T-helper (Th) 1 cytokines like IFNγ and also interleukin (IL)-4 (Th2), IL-17 (Th17), and IL-10. [30][31][32][33] These responses belong to the adaptive immune responses that facilitate and contribute to infection control and vaccination efficacy.…”

Section: The Concept Of Trained Immunity: a Novel Type Of Immune Memorymentioning

confidence: 99%

'Trained immunity: consequences for lymphoid malignancies

et al. 2016

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© Ferrata Storti Foundationhave no adaptive immune response, e.g., plants and invertebrates, but it also exists in humans, where it might be of special benefit in neonates that have yet to develop a mature adaptive immune repertoire.6 Importantly, 'training' of the innate immune system by the use of vaccination, resulting in increased immune activation, has been shown feasible. Hopefully these insights can be exploited in the near future for the design of new treatments for immunodeficiencies, infections and cancer.

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IL‐23‐dependent IL‐17 drives Th1‐cell responses following Mycobacterium bovis BCG vaccination

Cited by 147 publications

References 37 publications

MAIT cells are critical for optimal mucosal immune responses during in vivo pulmonary bacterial infection

MAIT cells are critical for optimal mucosal immune responses during in vivo pulmonary bacterial infection

Role of Th1/Th17 Balance Regulated by T-bet in a Mouse Model of Mycobacterium avium Complex Disease

'Trained immunity: consequences for lymphoid malignancies

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