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Originally published online as doi:10.2353/ajpath.2007.061006 on July 9, 2007

Published online before print July 9, 2007
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(American Journal of Pathology. 2007;171:571-579.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.061006

Tonsil Epithelial Factors May Influence Oropharyngeal Human Immunodeficiency Virus Transmission

Niki M. Moutsopoulos*, Salvador Nares*, Nikolaos Nikitakis{dagger}, Zoila Rangel{ddagger}, Jie Wen*, Peter Munson{ddagger}, John Sauk{dagger} and Sharon M. Wahl*

From the Oral Infection and Immunity Branch,* National Institute of Dental and Craniofacial Research, and the Mathematics and Statistical Computing Laboratory,{ddagger} Center for Information Technology, National Institutes of Health, Bethesda; and the Department of Diagnostic Sciences and Pathology and GreenBaum Cancer Center,{dagger} University of Maryland, Baltimore, Maryland

Tonsil epithelium has been implicated in human immunodeficiency virus (HIV) pathogenesis, but its role in oral transmission remains controversial. To study characteristics of this tissue, which may influence susceptibility or resistance to HIV, we performed microarray analysis of the tonsil epithelium. Our data revealed that genes related to immune functions such as antibody production and antigen processing were increasingly expressed in tonsil compared with the epithelium of another oropharyngeal site, the gingival epithelium. Importantly, tonsil epithelium highly expressed genes associated with HIV entrapment and/or transmission, including the HIV co-receptor CXCR4 and the potential HIV-binding molecules FcR{gamma}III, complement receptor 2, and various complement components. Immunohistochemical staining confirmed the increased presence of CXCR4 in the tonsil epithelium compared with multiple oral epithelial sites, particularly in basal and parabasal layers. This increased expression of molecules involved in viral recognition, binding, and entry may favor virus-epithelium interactions in an environment with reduced innate antiviral mechanisms. Specifically, secretory leukocyte protease inhibitor, an innate molecule with anti-HIV activity, was minimal in the tonsil epithelium, in contrast to oral mucosa. Collectively, our data suggest that increased expression of molecules associated with HIV binding and entry coupled with decreased innate antiviral factors may render the tonsil a potential site for oral transmission.




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