Chancellery Research - Research Publications

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Author: Corbett, Alexandra × Author: McCluskey, James × Author: Rossjohn, Jamie × End date: 2021 × Start date: 2020 ×

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    Francisella tularensis induces Th1 like MAIT cells conferring protection against systemic and local infection
    Zhao, Z ; Wang, H ; Shi, M ; Zhu, T ; Pediongco, T ; Lim, XY ; Meehan, BS ; Nelson, AG ; Fairlie, DP ; Mak, JYW ; Eckle, SBG ; Moreira, MDL ; Tumpach, C ; Bramhall, M ; Williams, CG ; Lee, HJ ; Haque, A ; Evrard, M ; Rossjohn, J ; McCluskey, J ; Corbett, AJ ; Chen, Z (NATURE PORTFOLIO, 2021-07-16)
    Mucosal-associated Invariant T (MAIT) cells are recognized for their antibacterial functions. The protective capacity of MAIT cells has been demonstrated in murine models of local infection, including in the lungs. Here we show that during systemic infection of mice with Francisella tularensis live vaccine strain results in evident MAIT cell expansion in the liver, lungs, kidney and spleen and peripheral blood. The responding MAIT cells manifest a polarised Th1-like MAIT-1 phenotype, including transcription factor and cytokine profile, and confer a critical role in controlling bacterial load. Post resolution of the primary infection, the expanded MAIT cells form stable memory-like MAIT-1 cell populations, suggesting a basis for vaccination. Indeed, a systemic vaccination with synthetic antigen 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil in combination with CpG adjuvant similarly boosts MAIT cells, and results in enhanced protection against both systemic and local infections with different bacteria. Our study highlights the potential utility of targeting MAIT cells to combat a range of bacterial pathogens.
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    Mucosal-associated invariant T cells promote inflammation and intestinal dysbiosis leading to metabolic dysfunction during obesity
    Toubal, A ; Kiaf, B ; Beaudoin, L ; Cagninacci, L ; Rhimi, M ; Fruchet, B ; da Silva, J ; Corbett, AJ ; Simoni, Y ; Lantz, O ; Rossjohn, J ; McCluskey, J ; Lesnik, P ; Maguin, E ; Lehuen, A (NATURE PORTFOLIO, 2020-07-24)
    Obesity is associated with low-grade chronic inflammation promoting insulin-resistance and diabetes. Gut microbiota dysbiosis is a consequence as well as a driver of obesity and diabetes. Mucosal-associated invariant T cells (MAIT) are innate-like T cells expressing a semi-invariant T cell receptor restricted to the non-classical MHC class I molecule MR1 presenting bacterial ligands. Here we show that during obesity MAIT cells promote inflammation in both adipose tissue and ileum, leading to insulin resistance and impaired glucose and lipid metabolism. MAIT cells act in adipose tissue by inducing M1 macrophage polarization in an MR1-dependent manner and in the gut by inducing microbiota dysbiosis and loss of gut integrity. Both MAIT cell-induced tissue alterations contribute to metabolic dysfunction. Treatment with MAIT cell inhibitory ligand demonstrates its potential as a strategy against inflammation, dysbiosis and metabolic disorders.