Caspase-12 and the inflammatory response to Yersinia pestis
Publication year
2009Source
PLoS One, 4, 9, (2009), article e6870ISSN
Publication type
Article / Letter to editor

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Organization
Internal Medicine
Paediatrics - OUD tm 2017
Gastroenterology
Neurology
Rheumatology
Medical Microbiology
Journal title
PLoS One
Volume
vol. 4
Issue
iss. 9
Subject
N4i 1: Pathogenesis and modulation of inflammation; NCEBP 13: Infectious diseases and international health; NCMLS 1: Infection and autoimmunityAbstract
BACKGROUND: Caspase-12 functions as an antiinflammatory enzyme inhibiting caspase-1 and the NOD2/RIP2 pathways. Due to increased susceptibility to sepsis in individuals with functional caspase-12, an early-stop mutation leading to the loss of caspase-12 has replaced the ancient genotype in Eurasia and a significant proportion of individuals from African populations. In African-Americans, it has been shown that caspase-12 inhibits the pro-inflammatory cytokine production. METHODOLOGY/PRINCIPAL FINDINGS: We assessed whether similar mechanisms are present in African individuals, and whether evolutionary pressures due to plague may have led to the present caspase-12 genotype population frequencies. No difference in cytokine induction through the caspase-1 and/or NOD2/RIP2 pathways was observed in two independent African populations, among individuals with either an intact or absent caspase-12. In addition, stimulations with Yersinia pestis and two other species of Yersinia were preformed to investigate whether caspase-12 modulates the inflammatory reaction induced by Yersinia. We found that caspase-12 did not modulate cytokine production induced by Yersinia spp. CONCLUSIONS: Our experiments demonstrate for the first time the involvement of the NOD2/RIP2 pathway for recognition of Yersinia. However, caspase-12 does not modulate innate host defense against Y. pestis and alternative explanations for the geographical distribution of caspase-12 should be sought.
This item appears in the following Collection(s)
- Academic publications [229134]
- Electronic publications [111496]
- Faculty of Medical Sciences [87758]
- Open Access publications [80317]
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