The impact of caspase-12 on susceptibility to candidemia.

Abstract

Candida is one of the leading causes of sepsis, and an effective host immune response to Candida critically depends on the cytokines IL-1β and IL-18, which need caspase-1 cleavage to become bioactive. Caspase-12 has been suggested to inhibit caspase-1 activation and has been implicated as a susceptibility factor for bacterial sepsis. In populations of African descent, CASPASE-12 is either functional or non-functional. Here, we have assessed the frequencies of both CASPASE-12 alleles in an African-American Candida sepsis patients cohort compared to uninfected patients with similar predisposing factors. African-American Candida sepsis patients (n = 93) and non-infected African-American patients (n = 88) were genotyped for the CASPASE-12 genotype. Serum cytokine concentrations of IL-6, IL-8, and IFNγ were measured in the serum of infected patients. Statistical comparisons were performed in order to assess the effect of the CASPASE-12 genotype on susceptibility to candidemia and on serum cytokine concentrations. Our findings demonstrate that CASPASE-12 does not influence the susceptibility to Candida sepsis, nor has any effect on the serum cytokine concentrations in Candida sepsis patients during the course of infection. Although the functional CASPASE-12 allele has been suggested to increase susceptibility to bacterial sepsis, this could not be confirmed in our larger cohort of fungal sepsis patients.

• Authors: D C Rosentul, T S Plantinga, W K Scott, B D Alexander, N M D van de Geer, J R Perfect, B J Kullberg, M D Johnson, M G Netea
• Journal: European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology (Eur J Clin Microbiol Infect Dis) Vol. 31 Issue 3 Pg. 277-80 (Mar 2012) ISSN: 1435-4373 [Electronic] Germany
• PMID: 21706251 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• Interleukin-8
• Interferon-gamma
• CASP12 protein, human
• Caspase 12

Topics

• Black or African American (genetics)
• Candida (pathogenicity)
• Candidemia (genetics)
• Caspase 12 (genetics)
• Disease Susceptibility
• Female
• Genetic Variation
• Genotype
• Humans
• Interferon-gamma (blood, genetics)
• Interleukin-6 (blood, genetics)
• Interleukin-8 (blood, genetics)
• Male
• Middle Aged
• Sepsis (blood, genetics)