Cathepsin C limits acute viral infection independently of NK cell and CD8+ T-cell cytolytic function

Christopher E. Andoniou, Peter Fleming, Vivien R. Sutton, Joseph A. Trapani, Mariapia A. Degli-Esposti

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5 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)540-548
Number of pages9
JournalImmunology and Cell Biology
Issue number4
Publication statusPublished - 1 May 2011


  • cathepsin c
  • cytomegalovirus
  • granzyme

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