Sir Peter MacCallum Department of Oncology - Research Publications

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Author: Wang, Nancy × Type: Journal Article ×

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    MAIT cells protect against pulmonary Legionella longbeachae infection
    Wang, H ; D'Souza, C ; Lim, XY ; Kostenko, L ; Pediongco, TJ ; Eckle, SBG ; Meehan, BS ; Shi, M ; Wang, N ; Li, S ; Liu, L ; Mak, JYW ; Fairlie, DP ; Iwakura, Y ; Gunnersen, JM ; Stent, AW ; Godfrey, DI ; Rossjohn, J ; Westall, GP ; Kjer-Nielsen, L ; Strugnell, RA ; McCluskey, J ; Corbett, AJ ; Hinks, TSC ; Chen, Z (NATURE RESEARCH, 2018-08-22)
    Mucosal associated invariant T (MAIT) cells recognise conserved microbial metabolites from riboflavin synthesis. Striking evolutionary conservation and pulmonary abundance implicate them in antibacterial host defence, yet their functions in protection against clinically important pathogens are unknown. Here we show that mouse Legionella longbeachae infection induces MR1-dependent MAIT cell activation and rapid pulmonary accumulation of MAIT cells associated with immune protection detectable in immunocompetent host animals. MAIT cell protection is more evident in mice lacking CD4+ cells, and adoptive transfer of MAIT cells rescues immunodeficient Rag2-/-γC-/- mice from lethal Legionella infection. Protection is dependent on MR1, IFN-γ and GM-CSF, but not IL-17A, TNF or perforin, and enhanced protection is detected earlier after infection of mice antigen-primed to boost MAIT cell numbers before infection. Our findings define a function for MAIT cells in protection against a major human pathogen and indicate a potential role for vaccination to enhance MAIT cell immunity.
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    NK cell intrinsic regulation of MIP-1α by granzyme M
    Baschuk, N ; Wang, N ; Watt, SV ; Halse, H ; House, C ; Bird, PI ; Strugnell, R ; Trapani, JA ; Smyth, MJ ; Andrews, DM (NATURE PUBLISHING GROUP, 2014-03)
    Granzymes are generally recognized for their capacity to induce various pathways of perforin-dependent target cell death. Within this serine protease family, Granzyme M (GrzM) is unique owing to its preferential expression in innate effectors such as natural killer (NK) cells. During Listeria monocytogenes infection, we observed markedly reduced secretion of macrophage inflammatory protein-1 alpha (MIP-1α) in livers of GrzM-deficient mice, which resulted in significantly impaired NK cell recruitment. Direct stimulation with IL-12 and IL-15 demonstrated that GrzM was required for maximal secretion of active MIP-1α. This effect was not due to reduced protein induction but resulted from heightened intracellular accumulation of MIP-1α, with reduced release. These results demonstrate that GrzM is a critical mediator of innate immunity that can regulate chemotactic networks and has an important role in the initiation of immune responses and pathogen control.