Role of Dectin-1/beta-glucan innate immune recognition during Candida albicans systemic infection.

VIGEZZI, CECILIA; RODRIGUEZ, EMILSE; ICELY, PAULA ALEJANDRA; MIRÓ, MARÍA SOLEDAD; RIERA, FERNANDO OSCAR; CAEIRO, JUAN PABLO; SOTOMAYOR, CLAUDIA ELENA

Congreso; 17th INFOCUS- 1ST ISHAM Latin American Congress; 2019

Invasive candidiasis is an important fungal infection associated with medical care.It is widely recognized as one of the main causes of morbidity and mortality in the healthcare environment, representing a great socio-economic impact on public health. This pathology can be caused by several Candida species, being C.albicans the most frequently found. The recognition of microorganisms by innate immune cells is a crucial event for the defense against fungal pathogens. In this scenario, the role of Dectin-1 receptor and its interaction with the β-glucans present in the fungal wall in the host defense against C. albicans, remain unclear. Objective: Our aim was to characterize the Dectin-1/β-glucan interaction in order to evaluate the impact of host and pathogen defective recognition in the outcome of C.albicans systemic infection. Methods: Male C57BL/6 (WT) and Dectin-1 Knock-out (KO)(Clec7a-/-) mice were injected intravenously (iv) with C.albicans SC5314 (parental strain) and identified as WT-SC5314 and KO-SC5314 groups respectively. Beside, Male C57BL/6 (WT) were iv infected with a beta-1,3-D-glucansintase defective strain, C. albicans-FKS1-S645 (WT-FKS645 group). All animals were inoculated with 2.5x106 yeast and at 4h, 12h, 24h, 48h, 7 and 15 days (d) post-infection (pi), the animals were sacrificed. Index of Body Weight (IBW), fungal burden (CFU), histological studies and survival of all animal groups were evaluated.Results: Animals of WT-SC5314 and WT-FKS645 groups showed similar profile of infection with significant decrease of IBW compared with WT-uninfected animals (4h,24h,7d p<0,05); however WT-FKS645 mice showed a major number of CFU in kidney than WT-SC5314 (24h p<0.05) and severe loss of tissue architecture, with tubular and glomeruli atrophy, abundant fungal invasion of renal pelvis and strong PMN cells infiltrate. Infected Dectin-1 deficient mice showed significant decreased of IBW compared with WT-SC5314 group (48h,7d p<0.05), and high levels of renal fungal burden (4h,12,14,48h p<0,05) with marked kidney hypertrophy compared to WT-SC5314 mice (7d p<0.01). Renal damage was characterized by loss of both normal tubular and glomeruli morphology, mass of C.albicans hyphae and large abscesses. Finally, the severity of infection in different infected groups was compared, meanwhile WT-SC5314 animals showed 50% of survival at 11d pi, this time was reduced in other groups. For WT-FKS645 animals 50% of survival was observed at 7d pi and at 6d pi for KO-SC5314 group. Conclusion: The partial or total absence of Dectin-1 pathway signaling, caused by both pathogen or host defective recognition is a crucial event for control of fungal invasion and severity of systemic infection by C.albicans.