Candida albicans exploits host eNOS to deregulate host immunity in a mouse model of disseminated candidiasis

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NCI	INFECTDIS-10

* FARE Award Winner

Authors

• D Navarathna
• S Amarnath
• M Lionakis
• D Roberts

Abstract

Endothelial nitric oxide synthase (eNOS) is constitutively expressed in endothelial cells of mammals, and its highly regulated activity to produce NO is an important regulator of the cardiovascular system. We studied the role of eNOS in a mouse model of disseminated candidiasis to examine the role of eNOS in a fungal infection. We found that eNOS null mice show a significantly higher survival rate compared with WT mice in a model of disseminated candidiasis. Histopathology confirmed that eNOS null mice successfully eliminated invading Candida from the renal cortex with mild inflammatory reactions. An examination of serum cytokines revealed significant elevations of IL-12, IL-17 and the chemokine GM-CSF in eNOS null mice compared with WT at 1, 3 and 5 days post infection . However, eNOS null mice showed significantly lower IL-6 levels compared with WT at 5 day post infection. eNOS null mice had significantly lower neutrophil accumulation in the Candida infected kidneys compared with the WT. We also found that eNOS null mice have significantly higher Th2 and Th17 cell numbers in the spleen compared with the WT. These results suggest that, an eNOS null background fosters a balanced immune response that is protective against disseminated candidiasis.

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