Title

Virulence characteristics and proinflammatory cytokine inducing potential of Candida glabrata in oral infection

Date of Completion

January 2009

Keywords

Biology, General|Health Sciences, Dentistry

Degree

Ph.D.

Abstract

Oral candidiasis is a common opportunistic infection in immunocompromised individuals, including individuals with HIV infections, transplant recipients and people receiving cancer therapy. Candida albicans (C. albicans) is the most prevalent etiologic agent associated with this infection. In the past two decades, Candida glabrata has emerged as a notable pathogenic agent in the oral mucosa, frequently being coioslated with C. albicans. Meanwhile, reports of C. glabrata as the sole detectable species from oral lesions have also been rising steadily. As the first line of defense Candida encounters during oral infection, oral mucosal epithelial cells play important roles in host defense against infection. Production of proinflammatory cytokines by these cells in response to Candida pathogens plays a critical role in the early activation of immuneffector cells including neutrophils and macrophages. Our studies investigated virulence characteristics and proinflammatory cytokine inducing potential of C. glabrata in oral infection, and the mechanisms by with local non-immune mucosal cells respond to C. glabrata by mounting a proinflammatory cytokine response. We found that C. glabrata strains demonstrated variable tissue damaging and invasive potential in oral infection, which was overall lower than that of C. albicans. Moreover, we also found that C. glabrata and C. albicans have significant differences in the proinflammatory cytokine profiles triggered in oral epithelial cells (OECs), with C. glabrata triggering a more pronounced GM-CSF and C. albicans triggering a more pronounced IL-8 and IL-1α response. Finally, we demonstrated that C. glabrata induced GM-CSF release from OECs was adhesion-dependent and enhanced by endocytosis. Interaction between C. glabrata and cell surface receptor CDw17, but not TLR4, induced the GM-CSF response in OECs through activation of nuclear factor kappa B (NF-κB). These data provide a better understanding of the host response and pathogenesis of oral mucosal C. glabrata infection. ^