Journal Article

Caspase-12 and the Inflammatory Response to Yersinia pestis

de Vries, Maaike C., van der Meer, Jos W. M., Joosten, Leo A. B., Reubsaet, Frans A. G., Daou, Modibo, McCall, Matthew B. B., Dolo, Amagana, Netea, Mihai G., Hopman, Joost, de Jong, Dirk, van der Ven, André J. A. M., Tissingh, Rudi A., Sauerwein, Robert, Ferwerda, Bart, Maiga, Boubacar, Doumbo, Ogobara

2009

Overview

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. 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: African Americans / Apoptosis / Bacterial infections / Caspase / Caspase 12 - physiology / Caspase-1 / Caspase-12 / Crohn's disease / Crohns disease / Cytokines / Cytokines - metabolism / Disease control / Disease susceptibility / Enzymes / Evolutionary Biology/Human Evolution / Gangrene / Gene expression / Gene Expression Regulation / Genotype / Geographical distribution / Gram-negative bacteria / Humans / Immune system / Immunity, Innate / Immunology/Genetics of the Immune System / Immunology/Innate Immunity / Infection / Infections / Infectious Diseases / Inflammation / Inflammatory response / Interleukin-1beta - metabolism / Laboratories / Mali / Mammals / Medicine / Minority & ethnic groups / Mutation / NOD2 protein / Nod2 Signaling Adaptor Protein - metabolism / Pathogenesis / Pathways / Phylogenetics / Plague / Polyclonal antibodies / Populations / Proteins / Public health / Receptor-Interacting Protein Serine-Threonine Kinase 2 - metabolism / Sepsis / Sepsis - metabolism / Tumor necrosis factor-TNF / Yersinia / Yersinia Infections - metabolism / Yersinia pestis - pathogenicity