Cell death mediated apoptosis by a Candida albicans infection in Central Nervous System

PERALTA RAMOS JM; FIGUEREDO CM; MAYOL G; MIRO MS; ICELY PA; CEJAS H; SOTOMAYOR CE

Huerta Grande, Cordoba

Congreso; XXVI Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias, Huerta Grande, Córdoba; 2011

Sociedad Argentina de Neurociencias

Neurocandidiasis is a serious form of bloodstream infection with 50% of mortality, associated with congenital or acquired immunodeficiencies. With the aim to explore the ethiopathogenic mechanisms involved in this mycosis, we developed a murine in vivo model. C57Bl/6 mice were injected iv with 5.105, 1.106 or 2,5.106 viable yeasts of C. albicans and the colonization assessed 4, 12, 24, 48 and 72h post-infection. Candida was able to impinge, get through the BBB and settle down in the brain parenchyma as was confirmed by the recovery of the CFU 4h after the microorganism administration. The immunostaining with anti-GFAP and anti-CD11b (Astrocytes and Microglia marker respectively), revealed the presence of both reactive astroand microgliosis (IF). Interestingly, we detected neuronal degeneration associated to the infection (FJB/A-Cu-Ag stain) and a significant number of TUNEL+ cells. The local balance between pro- (IL-1â and TNF-á) and anti-inflammatory (TGF-â and IL-10) cytokines indicated a break-up of the niche homeostasis promoting a Th1 profile (ELISA). This model reproduces human pathology and provides evidence not reported yet in support of neuronal degeneration and apoptosis+ and/or pyroptosis+ cells after a systemic induced infection with C. albicans.in vivo model. C57Bl/6 mice were injected iv with 5.105, 1.106 or 2,5.106 viable yeasts of C. albicans and the colonization assessed 4, 12, 24, 48 and 72h post-infection. Candida was able to impinge, get through the BBB and settle down in the brain parenchyma as was confirmed by the recovery of the CFU 4h after the microorganism administration. The immunostaining with anti-GFAP and anti-CD11b (Astrocytes and Microglia marker respectively), revealed the presence of both reactive astroand microgliosis (IF). Interestingly, we detected neuronal degeneration associated to the infection (FJB/A-Cu-Ag stain) and a significant number of TUNEL+ cells. The local balance between pro- (IL-1â and TNF-á) and anti-inflammatory (TGF-â and IL-10) cytokines indicated a break-up of the niche homeostasis promoting a Th1 profile (ELISA). This model reproduces human pathology and provides evidence not reported yet in support of neuronal degeneration and apoptosis+ and/or pyroptosis+ cells after a systemic induced infection with C. albicans.5, 1.106 or 2,5.106 viable yeasts of C. albicans and the colonization assessed 4, 12, 24, 48 and 72h post-infection. Candida was able to impinge, get through the BBB and settle down in the brain parenchyma as was confirmed by the recovery of the CFU 4h after the microorganism administration. The immunostaining with anti-GFAP and anti-CD11b (Astrocytes and Microglia marker respectively), revealed the presence of both reactive astroand microgliosis (IF). Interestingly, we detected neuronal degeneration associated to the infection (FJB/A-Cu-Ag stain) and a significant number of TUNEL+ cells. The local balance between pro- (IL-1â and TNF-á) and anti-inflammatory (TGF-â and IL-10) cytokines indicated a break-up of the niche homeostasis promoting a Th1 profile (ELISA). This model reproduces human pathology and provides evidence not reported yet in support of neuronal degeneration and apoptosis+ and/or pyroptosis+ cells after a systemic induced infection with C. albicans.+ cells. The local balance between pro- (IL-1â and TNF-á) and anti-inflammatory (TGF-â and IL-10) cytokines indicated a break-up of the niche homeostasis promoting a Th1 profile (ELISA). This model reproduces human pathology and provides evidence not reported yet in support of neuronal degeneration and apoptosis+ and/or pyroptosis+ cells after a systemic induced infection with C. albicans.â and TNF-á) and anti-inflammatory (TGF-â and IL-10) cytokines indicated a break-up of the niche homeostasis promoting a Th1 profile (ELISA). This model reproduces human pathology and provides evidence not reported yet in support of neuronal degeneration and apoptosis+ and/or pyroptosis+ cells after a systemic induced infection with C. albicans.+ and/or pyroptosis+ cells after a systemic induced infection with C. albicans.