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Faculty Anna Dongari-Bagtzoglou
Assistant Professor, Department of Oral Health and Diagnostic
Sciences, Division of Periodentology
adongari@uchc.edu
My laboratory examines host cell-parasite interactions that regulate
inflammation and innate immune cell function in oral opportunistic
infections. More specifically we are studying the regulation of cytokine
and inflammatory mediator synthesis by oral epithelial or connective
tissue cells following infectious challenge, and the mechanisms of
activation of phagocytes by such structural oral mucosal cells. Although
in the past our primary focus was on bacterial agents causing aggressive
forms of periodontitis, recently our focus has shifted towards host
cell-parasite interactions in oropharyngeal candidiasis. This infection
is the most frequent opportunistic infection associated with chronically
immunosuppressed states such as HIV infection or allotransplantation.
Candida albicans is the principal species responsible for intraoral
infections in these patient categories.
In the past years we have identified several cytokines that are
synthesized by primary human oral mucosal cell culture systems (gingival
epithelial cells, fibroblasts) including interleukins 1a, 1b, 6, 8 and
GM-CSF, upon challenge with oral C. albicans strains. We have also
investigated the role of yeast viability, germination into hyphae,
physical contact with oral mucosal cells, as well as intracellular
invasive capacity, in these cytokine-eliciting oral mucosal cell-fungal
interactions. Current investigations are aimed towards: a) defining the
role of salivary glycoproteins, also known as mucins, which can
strengthen the adhesive capacity of C. albicans to oral epithelial
cells, and further elucidating the specific Candida-oral mucosal cell
recognition systems that are involved in these interactions; and b)
defining the functional role of cytokines generated in our oral mucosal
cell-C. albicans coculture model systems in the innate immune cell
activation against fungal infection. Since the most important immune
effector cell in oral candidiasis is the neutrophil, we are
investigating whether cytokines released by oral mucosal cells following
fungal infection can enhance neutrophil chemotaxis, phagocytosis and
killing of fungal targets.
Future studies will investigate whether neutrophils isolated from
healthy and pharmacologically or HIV-immunosuppressed individuals can
respond similarly to these soluble immune mediators secreted by
structural oral mucosal cells. Identification of oral mucosal cell
cytokines with the ability to enhance anti-fungal activities of PMN from
immunocompromised patients may have therapeutic implications in the
treatment of this oral infection in the severely immunocompromised host
who is particularly prone to invasive or disseminated candidiasis. For
example, topical use of specific recombinant cytokines with neutrophil
activating potential, in combination with anti-fungal agents may become
the future treatment of choice in the extremely immunocompromised host
who suffers from oropharyngeal candidiasis.
Selected Publications:
Dongari-Bagtzoglou A.I., Cunha Villar C., Kashleva H., “Bioactive
IL-1a is cytolytically released from Candida albicans-infected oral
epithelial cells.” In Review “Medical Mycology”.
Dongari-Bagtzoglou AI, Thienel U., Yellin MJ. CD40 Ligation Triggers
COX-2 Expression in Endothelial Cells: Evidence that CD40-Mediated IL-6
Synthesis is COX-2-Dependent. Inflammation Research, 2003; 52(1):18-25.
Dongari-Bagtzoglou A.I., Kashleva H., “Candida albicans Triggers
Interleukin-8 Secretion by Oral Epithelial Cells.” Microbial
Pathogenesis, 2003; 34(4):169-177.
Dongari-Bagtzoglou AI, Kashleva H. “Granulocyte-macrophage
colony-stimulating factor responses of oral epithelial cells to Candida
albicans.” Oral Microbiology and Immunology, 2003; 18:165-170.
Sinha-Morton R., Dongari-Bagtzoglou AI. “Cyclooxygenase-2 Expression
is Upregulated in Inflamed Gingival Tissues.” Journal of Periodontology,
2001; 72:461-469. |
