Anna Dongari-Bagtzoglou
Assistant Professor, Department of Oral Health and Diagnostic
Sciences, Division of Periodontology
adongari@uchc.edu
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Areas of Interest
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. |
