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A pro‐survival role for the intracellular granzyme B inhibitor Serpinb9 in natural killer cells during poxvirus infection
Author(s) -
Mangan Matthew S,
MeloSilva Carolina R,
Luu Jennii,
Bird Catherina H,
Koskinen Aulikki,
Rizzitelli Alexandra,
Prakash Monica,
Scarff Katrina L,
Müllbacher Arno,
Regner Matthias,
Bird Phillip I
Publication year - 2017
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2017.59
Subject(s) - granzyme b , granzyme , intracellular , virology , biology , immunology , microbiology and biotechnology , immune system , perforin , cd8
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.