Abstract |
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.
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Authors | Christopher E Andoniou, Peter Fleming, Vivien R Sutton, Joseph A Trapani, Mariapia A Degli-Esposti |
Journal | Immunology and cell biology
(Immunol Cell Biol)
Vol. 89
Issue 4
Pg. 540-8
(May 2011)
ISSN: 1440-1711 [Electronic] United States |
PMID | 20975734
(Publication Type: Journal Article)
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Chemical References |
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Topics |
- Animals
- Antigens
(immunology)
- Cathepsin C
(genetics, metabolism)
- Cell Line
- Cytomegalovirus Infections
(immunology)
- Cytotoxicity, Immunologic
(genetics, immunology)
- Gene Deletion
- Killer Cells, Natural
(immunology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Muromegalovirus
(physiology)
- Neutrophils
(immunology)
- T-Lymphocytes, Cytotoxic
(immunology)
- Virus Replication
(genetics, immunology)
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