Format

Send to

Choose Destination
Infect Immun. 2016 May 24;84(6):1796-1805. doi: 10.1128/IAI.01526-15. Print 2016 Jun.

The Tick Protein Sialostatin L2 Binds to Annexin A2 and Inhibits NLRC4-Mediated Inflammasome Activation.

Author information

1
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
2
Institute of Human Virology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
3
Institute of Human Virology, Departments of Medicine and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
4
Departments of Pathology, Microbiology and Immunology and Orthopedic Surgery, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York, USA.
5
Inflammation Program and Division of Infectious Diseases, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.
6
Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
7
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
8
Faculty of Science, University of South Bohemia in České Budějovice, Budweis, Czech Republic.
9
Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Budweis, Czech Republic.
10
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA jpedra@som.umaryland.edu.

Abstract

Tick saliva contains a number of effector molecules that inhibit host immunity and facilitate pathogen transmission. How tick proteins regulate immune signaling, however, is incompletely understood. Here, we describe that loop 2 of sialostatin L2, an anti-inflammatory tick protein, binds to annexin A2 and impairs the formation of the NLRC4 inflammasome during infection with the rickettsial agent Anaplasma phagocytophilum Macrophages deficient in annexin A2 secreted significantly smaller amounts of interleukin-1β (IL-1β) and IL-18 and had a defect in NLRC4 inflammasome oligomerization and caspase-1 activation. Accordingly, Annexin a2-deficient mice were more susceptible to A. phagocytophilum infection and showed splenomegaly, thrombocytopenia, and monocytopenia. Providing translational support to our findings, better binding of annexin A2 to sialostatin L2 in sera from 21 out of 23 infected patients than in sera from control individuals was also demonstrated. Overall, we establish a unique mode of inflammasome evasion by a pathogen, centered on a blood-feeding arthropod.

PMID:
27045038
PMCID:
PMC4907130
DOI:
10.1128/IAI.01526-15
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center