Perforin and Granzymes Have Distinct Roles in Defensive Immunity and Immunopathology

102Citations
Citations of this article
60Readers
Mendeley users who have this article in their library.

Abstract

Successful control of viral infection requires the host to eliminate the infecting pathogen without causing overt immunopathology. Here we showed that perforin (Prf1) and granzymes (Gzms) have distinct roles in defensive immunity and immunopathology in a well-established model of viral infection. Both Prf1 and Gzms drastically affected the outcome of murine cytomegalovirus (MCMV) infection. Viral titres increased markedly in both Prf1-/- and Gzma-/-Gzmb-/- mice, but Gzma-/-Gzmb-/- mice recovered and survived infection, whereas Prf1-/- mice did not. Indeed, infected Prf1-deficient hosts developed a fatal hemophagocytic lymphohistiocytosis (HLH)-like syndrome. This distinction in outcome depended on accumulation of mononuclear cells and T cells in infected Prf1-/- mice. Importantly, blocking experiments that clearly identified tumor necrosis factor-α (TNF-α) as the principal contributor to the lethality observed in infected Prf1-/- mice provided support for the clinical potential of such an approach in HLH patients whose disease is triggered by viral infection. © 2006 Elsevier Inc. All rights reserved.

Author supplied keywords

Cite

CITATION STYLE

APA

van Dommelen, S. L. H., Sumaria, N., Schreiber, R. D., Scalzo, A. A., Smyth, M. J., & Degli-Esposti, M. A. (2006). Perforin and Granzymes Have Distinct Roles in Defensive Immunity and Immunopathology. Immunity, 25(5), 835–848. https://doi.org/10.1016/j.immuni.2006.09.010

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free