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- Title
Caspase-12 and the Inflammatory Response to Yersinia pestis.
- Authors
Ferwerda, Bart; McCall, Matthew B. B.; de Vries, Maaike C.; Hopman, Joost; Maiga, Boubacar; Dolo, Amagana; Doumbo, Ogobara; Daou, Modibo; de Jong, Dirk; Joosten, Leo A. B.; Tissingh, Rudi A.; Reubsaet, Frans A. G.; Sauerwein, Robert; van der Meer, Jos W. M.; van der Ven, André J. A. M.; Netea, Mihai G.
- Abstract
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.
- Subjects
GENETICS of yersinia diseases; ANTI-inflammatory agents; ENZYMES; DISEASE susceptibility; SEPSIS; GENOTYPE-environment interaction
- Publication
PLoS ONE, 2009, Vol 4, Issue 9, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0006870