title: Caspase-12 deficiency enhances cytokine responses but does not protect against lethal Plasmodium yoelii 17XL infection.
abstract: To investigate the effect of caspase-12 deficiency on IFN-γ- independent control of blood-stage malaria, we compared lethal Plasmodium yoelii 17XL infection in wild-type C57BL ⁄ 6J and caspase-12-/-mice. Infected caspase-12-/- mice exhibited higher parasitaemia than WT mice on days 8 and 9 post-inoculation, but all WT and caspase-12-/- mice succumbed by day 10. In addition, infected caspase-12-/-mice had significantly elevated levels of IFN-γ, TNF, IL-18,and IL-10 in sera compared to infected WT mice. At the terminal stage of disease, there were no differences in cytokine levels in the tissues of infected WT and caspase-12-/- mice. However, liver pathology was more severe in infected caspase-12-/- mice compared to infected WT mice. Together, these findings indicate that although caspase-12 deficiency results in enhanced pro-inflammatory and immunoregulatory cytokine levels in sera during P. yoelii 17XL infection, these responses are not essential for protection against lethal malaria infection.
authors.affiliation: Centre for the Study of Host Resistance, Department of Medicine, McGill University, Montreal, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Miu
authors.forename: M
authors.initials: M
authors.lastname: Saleh
authors.forename: M M
authors.initials: MM
authors.lastname: Stevenson
mesh_terms: D000818:Animals; D053454:Caspase 12 / Q000172:deficiency / Q000276:immunology*; D016207:Cytokines / Q000097:blood*; D005260:Female; D008099:Liver / Q000473:pathology; D008288:Malaria / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018512:Parasitemia; D010967:Plasmodium yoelii / Q000276:immunology* / Q000472:pathogenicity*; D016019:Survival Analysis
chemical_list: D016207:Cytokines; C506440:Casp12 protein, mouse; D053454:Caspase 12