Granzyme A is critical for recovery of mice from infection with the natural cytopathic viral pathogen, ectromelia.

Müllbacher, Arno; Ebnet, Klaus; Blanden, Robert V.; Hla, Ron Tha; Stehlé, Thomas; Museteanu, C; Simon, Markus M.

doi:10.1073/pnas.93.12.5783

Cited by 129 publications

(116 citation statements)

References 21 publications

(23 reference statements)

Supporting

Mentioning

113

Contrasting

Order By: Relevance

“…Although the role of grzA in CTL killing is less well defined than that of grzB, grzA-deficient mice demonstrate increased susceptibility to ectromelia virus infection [15], highlighting grzA participation in immunity to natural host-pathogen interactions. Recently, an intriguing function for grzA in eliciting inflammation has been described.…”

Section: Frontlinementioning

confidence: 99%

Granzyme A expression reveals distinct cytolytic CTL subsets following influenza A virus infection

et al. 2009

View full text Add to dashboard Cite

CTL mediate anti-viral immunity via targeted exocytosis of cytolytic granules containing perforin and members of the granzyme (grz) serine protease family. Here, we provide the first analysis of grzA protein expression by murine anti-viral CTL. During the progression of influenza A virus infection, CTL expressed two divergent cytolytic phenotypes: grzA À B 1 and grzA 1 B 1 . CTL lacked grzA expression during the initial rounds of antigen-driven division. High levels of grzA were expressed by influenza-specific CTL early post infection (day 6), particularly in tissues associated with the infected respiratory tract (bronchoalveolar lavage, lung). Following resolution of influenza infection, a small population of memory CTL expressed grzA. Interestingly, individual influenza A virus-derived epitopespecific CTL expressed different levels of grzA. The grzA expression hierarchy was determined to be K b PB1 703 5 D b F2 62 5 K b NS2 114 4D b NP 366 5 D b PA 224 and inversely correlated with CTL magnitude. Therefore following influenza infection, a CTL cytolytic hierarchy was established relating to the different profiles of antigen expression and relative immunodominance. Analysis of CTL grzA expression during influenza virus immunity has enabled a more detailed insight into the cytolytic mechanisms of virus elimination.

show abstract

Section: Frontlinementioning

confidence: 99%

Granzyme A expression reveals distinct cytolytic CTL subsets following influenza A virus infection

et al. 2009

View full text Add to dashboard Cite

show abstract

“…71 The exceptions are the response to poxvirus ectromelia, where mice displayed a delayed clearance of the virus, and during herpes simplex infection, where virus spreads more readily throughout the peripheral nervous system. 72,73 Work recently published by Chris Froelich's group has suggested that GrA can only induce cell death at 'non-physiological levels', and that the primary function of GrA is actually the elicitation of inflammation. 74 Granzyme K. GrK was discovered and purified from LAK cells.…”

Section: Mechanisms Of Cytotoxicity and Physiological Roles Of Grsmentioning

confidence: 99%

A quarter century of granzymes

2011

View full text Add to dashboard Cite

show abstract

“…73,74 The idea that high levels of circulating granzyme A are associated with overactivation of the immune system is also borne out by studies that have identified increased levels of this protease in patients with persistent HIV infection or acute cytomegalovirus and Epstein-Barr virus infection, and this could reflect increased CTL/NK activity and impaired clearance of dead cytotoxic cells. 26,75,76 Extracellular substrates for granzyme A are only beginning to emerge (Table 1); however, it is possible that proteolysis of cell surface proteins by circulating granzyme A may mediate some of the damage seen in proinflammatory disease states associated with this enzyme. 77 Although granzyme A was observed to promote cytokine release from monocytes and to cleave and possibly activate the proinflammtory cytokine IL-1b over 20 years ago, a causal link between high levels of circulating granzyme A and the propagation of proinflammatory conditions was not fully appreciated until recently.…”

Section: Extracellular Role Of Granzymes In Immune Reactionsmentioning

confidence: 99%