Candida albicans triggers the caspase-1 pathway during

MAYOL G; VIGEZZI C; CEJAS H; ICELY PA; SOTOMAYOR CE

Los Cocos. Cordoba

Congreso; LXI Reunion Cientifica anual de la Sociedad Argentina de Inmunologia; 2013

Socieda Argentina de Inmunologia

Interleukin-1â is an important cytokine involved in the control of the fungus Candida albicans. This cytokine is predominantly produced by the innate immune cells through the recruitment and activation of intracellular proteins complex called inflammasome, which controls the activation of caspase-1 and the cleavage of proIL-1â, followed by release of the active mature IL-1â. The aim of this work is to study the IL-1â Caspase-1 pathway in the CNS during infection by C. albicans. C57BL/6 mice were infected intravenously with 2.5 x106 C. albicans (ATCC 36801), and at 12, 24, 48 and 72 hours were sacrificed and their brains were removed to assess: fungal burden (UFC), histological changes (PAS and HE stain), expression of Caspase-1 and IL-1â (IF) and in situ production of cytokine (ELISA). At 12h after inoculation, the fungus was recovered from the brain of infected animals (p<0.01); histological studies reveals the presence of invasive morphotype of C. albicans (hyphae) and absence of inflammatory infiltrate. Brain sections were stained using specific conjugated antibodies against Caspase-1 (FITC) and IL-1â (PE) and nuclei were stained with DAPI. The microscopic observation revealed immune positive foci distributed in the cerebral parenchyma; intracytoplasmic stain and co-localization of both molecules can be detected at major magnification. The kinetic study of intracerebral production of IL-1â revealed increased levels of cytokine compared to non-infected animals with a maximum at 12h post-infection (3874pg/g) (p<0.05). This work demonstrated the intracerebral production of an important pro-inflammatory cytokine through the recruitment and activation of Caspase-1 pathway in response to brain fungus arrives.