NK cell intrinsic regulation of MIP-1alpha by granzyme M

Nikola Baschuk, Nancy Wang, Sally V Watt, Heloise M Halse, Colin M House, Phillip Ian Bird, Richard Anthony Strugnell, Joseph A Trapani, Mark Smyth, Daniel M Andrews

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

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-1alpha) 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-1alpha. This effect was not due to reduced protein induction but resulted from heightened intracellular accumulation of MIP-1alpha, 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.
Original languageEnglish
Pages (from-to)1 - 11
Number of pages11
JournalCell Death and Disease
Volume5
Issue number3 (Art. No.: e1115)
DOIs
Publication statusPublished - 2014

Cite this

Baschuk, N., Wang, N., Watt, S. V., Halse, H. M., House, C. M., Bird, P. I., ... Andrews, D. M. (2014). NK cell intrinsic regulation of MIP-1alpha by granzyme M. Cell Death and Disease, 5(3 (Art. No.: e1115)), 1 - 11. https://doi.org/10.1038/cddis.2014.74
Baschuk, Nikola ; Wang, Nancy ; Watt, Sally V ; Halse, Heloise M ; House, Colin M ; Bird, Phillip Ian ; Strugnell, Richard Anthony ; Trapani, Joseph A ; Smyth, Mark ; Andrews, Daniel M. / NK cell intrinsic regulation of MIP-1alpha by granzyme M. In: Cell Death and Disease. 2014 ; Vol. 5, No. 3 (Art. No.: e1115). pp. 1 - 11.
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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-1alpha) 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-1alpha. This effect was not due to reduced protein induction but resulted from heightened intracellular accumulation of MIP-1alpha, 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.",
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Baschuk, N, Wang, N, Watt, SV, Halse, HM, House, CM, Bird, PI, Strugnell, RA, Trapani, JA, Smyth, M & Andrews, DM 2014, 'NK cell intrinsic regulation of MIP-1alpha by granzyme M', Cell Death and Disease, vol. 5, no. 3 (Art. No.: e1115), pp. 1 - 11. https://doi.org/10.1038/cddis.2014.74

NK cell intrinsic regulation of MIP-1alpha by granzyme M. / Baschuk, Nikola; Wang, Nancy; Watt, Sally V; Halse, Heloise M; House, Colin M; Bird, Phillip Ian; Strugnell, Richard Anthony; Trapani, Joseph A; Smyth, Mark; Andrews, Daniel M.

In: Cell Death and Disease, Vol. 5, No. 3 (Art. No.: e1115), 2014, p. 1 - 11.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Baschuk, Nikola

AU - Wang, Nancy

AU - Watt, Sally V

AU - Halse, Heloise M

AU - House, Colin M

AU - Bird, Phillip Ian

AU - Strugnell, Richard Anthony

AU - Trapani, Joseph A

AU - Smyth, Mark

AU - Andrews, Daniel M

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AB - 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-1alpha) 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-1alpha. This effect was not due to reduced protein induction but resulted from heightened intracellular accumulation of MIP-1alpha, 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.

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Baschuk N, Wang N, Watt SV, Halse HM, House CM, Bird PI et al. NK cell intrinsic regulation of MIP-1alpha by granzyme M. Cell Death and Disease. 2014;5(3 (Art. No.: e1115)):1 - 11. https://doi.org/10.1038/cddis.2014.74