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Cathepsin C limits acute viral infection independently of NK cell and CD8 + T‐cell cytolytic function
Author(s) -
Andoniou Christopher E,
Fleming Peter,
Sutton Vivien R,
Trapani Joseph A,
DegliEsposti Mariapia A
Publication year - 2010
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.2010.115
Subject(s) - granzyme , biology , proteases , cytotoxic t cell , perforin , cytolysis , granzyme b , cd8 , t cell , immunology , virology , immune system , in vitro , enzyme , biochemistry
Destruction of target cells by cytotoxic T lymphocytes (CTLs) or natural killer (NK) cells requires the coordinated action of the pore forming protein perforin (Pfp) and the granzyme (Gzm) family of serine proteases. The activation of a number of serine proteases, including GzmA and B, is predominately mediated by cathepsin C (CatC). Deficiencies in CatC‐null mice were therefore expected to replicate the defects observed in GzmAB‐deficient mice. We have previously determined that GzmAB‐deficient mice exhibit increased susceptibility to murine cytomegalovirus (MCMV) infection. Here, we have compared the ability of CatC −/− mice to control MCMV infection with that of GzmAB‐deficient animals. We found that CatC −/− mice have organ‐specific defects in the ability to control MCMV replication, a phenotype that is distinct to that observed in GzmAB −/− mice. Significantly, the cytolytic function of CatC‐deficient NK cells and CTLs elicited during infection was indistinguishable from that of wild‐type cells. Hence, CatC is involved in limiting MCMV replication; however, this effect is independent of its role in promoting effector cytolytic activity. These data provide evidence for a novel and unexpected role of CatC during viral infection.