Granzyme A in Chikungunya and Other Arboviral Infections

Granzyme A in Chikungunya and Other Arboviral Infections

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 vir...

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Bibliographic Details
Published in:Frontiers in immunology Vol. 10; p. 3083
Main Authors: Schanoski, Alessandra S, Le, Thuy T, Kaiserman, Dion, Rowe, Caitlin, Prow, Natalie A, Barboza, Diego D, Santos, Cliomar A, Zanotto, Paolo M A, Magalhães, Kelly G, Aurelio, Luigi, Muller, David, Young, Paul, Zhao, Peishen, Bird, Phillip I, Suhrbier, Andreas
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 14-01-2020
Subjects:
arbovirus
arthritis
chikungunya
granzyme A
Immunology
NK cell
granzyme A
arthritis
chikungunya
NK cell
arbovirus
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Summary: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.
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These authors share last authorship
Edited by: Lisa F. P. Ng, Singapore Immunology Network (A*STAR), Singapore
Reviewed by: Pierre Roques, CEA Saclay, France; Julian Pardo, Fundacion Agencia Aragonesa para la Investigacion y el Desarrollo, Spain
This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology
These authors share first authorship
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2019.03083