A pro-survival role for the intracellular granzyme B inhibitor Serpinb9 in natural killer cells during poxvirus infection

Matthew S. Mangan, Carolina R. Melo-Silva, Jennii Luu, Catherina H. Bird, Aulikki Koskinen, Alexandra Rizzitelli, Monica Prakash, Katrina L. Scarff, Arno Müllbacher, Matthias Regner, Phillip I. Bird

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Intracellular serpins are proposed to inactivate proteases released from lysosome-related organelles into the host cell interior, preventing cell death. Serpinb9 opposes the immune cytotoxic protease, granzyme B, and in a number of settings protects cells against granzyme B-mediated cell death. Using a knockout mouse line engineered to express green fluorescent protein under the serpbinb9 promoter, we demonstrate that serpinb9 is vital for host survival during Ectromelia virus infection by maintaining both mature natural killer NK) cells, and activated CD8 + T cells. Serpinb9 expression parallels granzyme B expression within both populations during infection. Maturing serpinb9-null NK cells exhibit higher levels of granzyme B-mediated apoptosis during infection; hence there are fewer mature NK cells, and these cells also have lower cytotoxic potential. Thus the serpinb9-granzyme B axis is important for homeostasis of both major cytotoxic effector cell populations.

Original languageEnglish
Pages (from-to)884-894
Number of pages11
JournalImmunology and Cell Biology
Volume95
Issue number10
DOIs
Publication statusPublished - 1 Nov 2017

Cite this

Mangan, Matthew S. ; Melo-Silva, Carolina R. ; Luu, Jennii ; Bird, Catherina H. ; Koskinen, Aulikki ; Rizzitelli, Alexandra ; Prakash, Monica ; Scarff, Katrina L. ; Müllbacher, Arno ; Regner, Matthias ; Bird, Phillip I. / A pro-survival role for the intracellular granzyme B inhibitor Serpinb9 in natural killer cells during poxvirus infection. In: Immunology and Cell Biology. 2017 ; Vol. 95, No. 10. pp. 884-894.
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abstract = "Intracellular serpins are proposed to inactivate proteases released from lysosome-related organelles into the host cell interior, preventing cell death. Serpinb9 opposes the immune cytotoxic protease, granzyme B, and in a number of settings protects cells against granzyme B-mediated cell death. Using a knockout mouse line engineered to express green fluorescent protein under the serpbinb9 promoter, we demonstrate that serpinb9 is vital for host survival during Ectromelia virus infection by maintaining both mature natural killer NK) cells, and activated CD8 + T cells. Serpinb9 expression parallels granzyme B expression within both populations during infection. Maturing serpinb9-null NK cells exhibit higher levels of granzyme B-mediated apoptosis during infection; hence there are fewer mature NK cells, and these cells also have lower cytotoxic potential. Thus the serpinb9-granzyme B axis is important for homeostasis of both major cytotoxic effector cell populations.",
author = "Mangan, {Matthew S.} and Melo-Silva, {Carolina R.} and Jennii Luu and Bird, {Catherina H.} and Aulikki Koskinen and Alexandra Rizzitelli and Monica Prakash and Scarff, {Katrina L.} and Arno M{\"u}llbacher and Matthias Regner and Bird, {Phillip I.}",
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Mangan, MS, Melo-Silva, CR, Luu, J, Bird, CH, Koskinen, A, Rizzitelli, A, Prakash, M, Scarff, KL, Müllbacher, A, Regner, M & Bird, PI 2017, 'A pro-survival role for the intracellular granzyme B inhibitor Serpinb9 in natural killer cells during poxvirus infection', Immunology and Cell Biology, vol. 95, no. 10, pp. 884-894. https://doi.org/10.1038/icb.2017.59

A pro-survival role for the intracellular granzyme B inhibitor Serpinb9 in natural killer cells during poxvirus infection. / Mangan, Matthew S.; Melo-Silva, Carolina R.; Luu, Jennii; Bird, Catherina H.; Koskinen, Aulikki; Rizzitelli, Alexandra; Prakash, Monica; Scarff, Katrina L.; Müllbacher, Arno; Regner, Matthias; Bird, Phillip I.

In: Immunology and Cell Biology, Vol. 95, No. 10, 01.11.2017, p. 884-894.

Research output: Contribution to journalArticleResearchpeer-review

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