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Infect Immun. 2019 Apr 23;87(5). pii: e00031-19. doi: 10.1128/IAI.00031-19. Print 2019 Mar.

A Phenome-Wide Association Study Uncovers a Pathological Role of Coagulation Factor X during Acinetobacter baumannii Infection.

Author information

1
Department of Pathology, Microbiology, & Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
2
Graduate Program in Microbiology & Immunology, Vanderbilt University, Nashville, Tennessee, USA.
3
Department of Pediatrics and the Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
4
Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
5
Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
6
Department of Pathology, Microbiology, & Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA eric.skaar@vumc.org.
7
Vanderbilt Institute for Infection, Immunology & Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Abstract

Coagulation and inflammation are interconnected, suggesting that coagulation plays a key role in the inflammatory response to pathogens. A phenome-wide association study (PheWAS) was used to identify clinical phenotypes of patients with a polymorphism in coagulation factor X. Patients with this single nucleotide polymorphism (SNP) were more likely to be hospitalized with hemostatic and infection-related disorders, suggesting that factor X contributes to the immune response to infection. To investigate this, we modeled infections by human pathogens in a mouse model of factor X deficiency. Factor X-deficient mice were protected from systemic Acinetobacter baumannii infection, suggesting that factor X plays a role in the immune response to A. baumannii Factor X deficiency was associated with reduced cytokine and chemokine production and alterations in immune cell population during infection: factor X-deficient mice demonstrated increased abundance of neutrophils, macrophages, and effector T cells. Together, these results suggest that factor X activity is associated with an inefficient immune response and contributes to the pathology of A. baumannii infection.

KEYWORDS:

Acinetobacter ; PheWAS; coagulation; innate immunity

PMID:
30782860
PMCID:
PMC6479028
[Available on 2019-10-23]
DOI:
10.1128/IAI.00031-19

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