title: NK cell intrinsic regulation of MIP-1α by granzyme M.
abstract: 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.
authors.affiliation: Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria 3002, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Baschuk
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Wang
authors.affiliation: Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria 3002, Australia.
authors.forename: S V
authors.initials: SV
authors.lastname: Watt
authors.affiliation: Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria 3002, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Halse
authors.affiliation: Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria 3002, Australia.
authors.forename: C
authors.initials: C
authors.lastname: House
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria 3800, Australia.
authors.forename: P I
authors.initials: PI
authors.lastname: Bird
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Strugnell
authors.affiliation: 1] Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria 3002, Australia [2] Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia [3] Sir Peter MacCallum Department of Oncology, The University of MelbourneParkville, Victoria 3010, Australia.
authors.forename: J A
authors.initials: JA
authors.lastname: Trapani
authors.affiliation: 1] Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria 3002, Australia [2] Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia [3] Sir Peter MacCallum Department of Oncology, The University of MelbourneParkville, Victoria 3010, Australia [4] Immunology in Cancer and Infection Laboratory, Queensland Institute of Medical Research, Herston Qld 4006, Australia [5] School of Medicine, University of Queensland, Herston Qld 4006, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Smyth
authors.affiliation: 1] Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria 3002, Australia [2] Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia [3] Sir Peter MacCallum Department of Oncology, The University of MelbourneParkville, Victoria 3010, Australia.
authors.forename: D M
authors.initials: DM
authors.lastname: Andrews
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D018920:Coculture Techniques; D004195:Disease Models, Animal; D053804:Granzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007378:Interleukins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D008089:Listeria monocytogenes / Q000276:immunology / Q000472:pathogenicity; D008088:Listeriosis / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D013997:Time Factors
chemical_list: C515429:CCL3 protein, human; C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D007378:Interleukins; C509218:GZMM protein, human; D053804:Granzymes; C509214:Gzmb protein, mouse; C509219:Gzmm protein, mouse