MR1-restricted mucosal-associated invariant T (MAIT) cells respond to mycobacterial vaccination and infection in nonhuman primates

Greene, Justin M.; Dash, Pradyot; Roy, Sudip; McMurtrey, Curtis P.; Awad, Walid; Reed, Jason S.; Hammond, Katherine B.; Abdulhaqq, Shaheed; Wu, Helen L.; Burwitz, Ben J.; Roth, B F; Morrow, David W.; Ford, Julia C.; Xu, Guangwu; Bae, Jin Young; Crank, Hugh; Legasse, Alfred W.; Dang, Thurston H. Y.; Greenaway, Hui Yee; Kurniawan, Monica; Gold, Marielle C.; Harriff, Melanie J.; Lewinsohn, Deborah A.; Park, B S; Axthelm, Michael K.; Stanton, Jeffrey J.; Hansen, Scott G.; Picker, Louis J.; Venturi, Vanessa; Hildebrand, William H.; Thomas, Paul G.; Adams, Erin J.; Sacha, Jonah B.

doi:10.1038/mi.2016.91

Cited by 96 publications

(158 citation statements)

References 44 publications

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“…This protective effect is encouraging for further investigations of other vaccine strategies based on innate-like T cells. For MAIT cells, the mouse study supports the protection of MAIT cells in M. abscessus -infected mice (20) and a newly published study shows the upregulation of cytotoxic MAIT cells in BCG-vaccinated macaque (206). In humans, high frequency of MAIT cells in latent infections of tuberculosis or healthy donors and low frequency in active tuberculosis support the association of high MAIT cell frequency with healthy conditions (12).…”

Section: Therapeutic Value and Remaining Questionsmentioning

confidence: 84%

Targeting Innate-Like T Cells in Tuberculosis

Huang

2016

Front. Immunol.

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Peptide-specific conventional T cells have been major targets for designing most antimycobacterial vaccines. Immune responses mediated by conventional T cells exhibit a delayed onset upon primary infection and are highly variable in different human populations. In contrast, innate-like T cells quickly respond to pathogens and display effector functions without undergoing extensive clonal expansion. Specifically, the activation of innate-like T cells depends on the promiscuous interaction of highly conserved antigen-presenting molecules, non-peptidic antigens, and likely semi-invariant T cell receptors. In antimicrobial immune responses, mucosal-associated invariant T cells are activated by riboflavin precursor metabolites presented by major histocompatibility complex-related protein I, while lipid-specific T cells including natural killer T cells are activated by lipid metabolites presented by CD1 proteins. Multiple innate-like T cell subsets have been shown to be protective or responsive in mycobacterial infections. Through rapid cytokine secretion, innate-like T cells function in early defense and memory response, offering novel advantages over conventional T cells in the design of anti-tuberculosis strategies.

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Section: Therapeutic Value and Remaining Questionsmentioning

confidence: 84%

Targeting Innate-Like T Cells in Tuberculosis

Huang

2016

Front. Immunol.

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“…MAIT cells are capable of recognizing Mtb-infected cells[20] and MAIT cells have been shown in a mice model to contribute to the early protection against Mtb infection[21]. MAIT cells have also been shown to respond to both Bacillus Calmette-Guerin vaccination and Mtb infection in a non-human primate model[47]. Therefore, the reduced frequency and functionality of MAIT cells that we observed in HTLV-1-infected subject could contribute to their increased susceptibility to Mtb.…”

Section: Discussionmentioning

confidence: 99%

MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection: Potential clinical implications

et al. 2017

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HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develop HAM/TSP. The cellular immune response has been implicated in the development of inflammatory alterations in these patients; however the pathogenic mechanisms for disease progression remain unclear. Furthermore, HTLV-1-infected individuals have an increase incidence of Mycobacterium tuberculosis (Mtb) infection, suggesting that immunological defect are associated with HTLV-1 infection. Evidence suggests an important role for Mucosal-associated invariant T (MAIT) cells in the early control of Mtb infection. Chronic viral infections like HIV and HCV have been associated with decreased frequency and functionality of MAIT cells. We hypothesized that HTLV-1 infection is associated with similar perturbations in MAIT cells. We investigated MAIT cell frequency, phenotype, and function by flow cytometry in a cohort of 10 asymptomatic and 10 HAM/TSP HTLV-1 infected patients. We found that MAIT cells from HTLV-1-infected subjects were reduced and showed high co-expression of the activation markers CD38 and HLA-DR but normal levels of CCR6 and CD127. MAIT cells had a lower expression of the transcription factor PLZF in HAM/TSP patients. Unlike Tax-specific CD8+T cells, which are hyperfunctional, MAIT cells from HTLV-1-infected subjects had a poor IFNγ response following antigen stimulation. MAIT cell perturbations in HTLV-1 infection were not associated with HTLV-1 proviral load and MAIT cells were not infected by HTLV-1 in vivo. Rather, MAIT cells loss was associated with immune activation. Overall, our results do not support a role for MAIT cells in HAM/TSP pathogenesis but reduced numbers of MAIT cells, together with their poor functionality, could contribute to the increased susceptibility of HTLV-1-infected individuals to other infectious agents.

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“…Additionally, Greene et al evaluated the in vivo response by MAIT cells to mycobacteria in NHP. Here, Greene et al used an MR1 tetramer to track MAIT cells in NHP that were vaccinated intradermally with BCG and then challenged with pulmonary Mtb 48 . They observed an increase in Ki-67 expression, a cellular marker of proliferation and activation, on MAIT cells at the site of vaccination and systemically during Mtb infection.…”

Section: Mechanisms By Which Mait Cells Influence Immunity To Bacterimentioning

confidence: 99%

MAIT cells and microbial immunity

et al. 2018

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Mucosal-associated invariant T (MAIT) cells, the most abundant T-cell subset in humans, are increasingly being recognized for their importance in microbial immunity. MAIT cells accumulate in almost every mucosal tissue examined, including the lung, liver and intestinal tract, where they can be activated through T-cell receptor (TCR) triggering as well as cytokine stimulation in response to a host of microbial products. In this review, we specifically discuss MAIT cell responses to bacterial and fungal infections, with a focus on responses that are both MR1-dependent and -independent, the evidence for diversity in MAIT TCR usage in response to discrete microbial products, protective immunity induced by MAIT cells, and MAIT cell antimicrobial functions in the context of these infections.

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MR1-restricted mucosal-associated invariant T (MAIT) cells respond to mycobacterial vaccination and infection in nonhuman primates

Cited by 96 publications

References 44 publications

Targeting Innate-Like T Cells in Tuberculosis

Targeting Innate-Like T Cells in Tuberculosis

MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1 infection: Potential clinical implications

MAIT cells and microbial immunity

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