Granzyme A in Chikungunya and Other Arboviral Infections

Alessandra S. Schanoski, Thuy T. Le, Dion Kaiserman, Caitlin Rowe, Natalie A. Prow, Diego D. Barboza, Cliomar A. Santos, Paolo M.A. Zanotto, Kelly G. Magalhães, Luigi Aurelio, David Muller, Paul Young, Peishen Zhao, Phillip I. Bird, Andreas Suhrbier

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Abstract

Granzyme A (GzmA) is secreted by cytotoxic lymphocytes and has traditionally been viewed as a mediator of cell death. However, a growing body of data suggests the physiological role of GzmA is promotion of inflammation. Here, we show that GzmA is significantly elevated in the sera of chikungunya virus (CHIKV) patients and that GzmA levels correlated with viral loads and disease scores in these patients. Serum GzmA levels were also elevated in CHIKV mouse models, with NK cells the likely source. Infection of mice deficient in type I interferon responses with CHIKV, Zika virus, or dengue virus resulted in high levels of circulating GzmA. We also show that subcutaneous injection of enzymically active recombinant mouse GzmA was able to mediate inflammation, both locally at the injection site as well as at a distant site. Protease activated receptors (PARs) may represent targets for GzmA, and we show that treatment with PAR antagonist ameliorated GzmA- and CHIKV-mediated inflammation.

Original languageEnglish
Article number3083
Number of pages14
JournalFrontiers in Immunology
Volume10
DOIs
Publication statusPublished - 14 Jan 2020

Keywords

  • arbovirus
  • arthritis
  • chikungunya
  • granzyme A
  • NK cell

Cite this

Schanoski, A. S., Le, T. T., Kaiserman, D., Rowe, C., Prow, N. A., Barboza, D. D., Santos, C. A., Zanotto, P. M. A., Magalhães, K. G., Aurelio, L., Muller, D., Young, P., Zhao, P., Bird, P. I., & Suhrbier, A. (2020). Granzyme A in Chikungunya and Other Arboviral Infections. Frontiers in Immunology, 10, [3083]. https://doi.org/10.3389/fimmu.2019.03083