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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0900640v1 183/11/7420    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Ju, C.-H. Articles by Leifer, C. A. PubMed PubMed Citation Articles by Ju, C.-H. Articles by Leifer, C. A.

Early Response of Mucosal Epithelial Cells during Toxoplasma gondii Infection

Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853

The innate immune response of mucosal epithelial cells during pathogen invasion plays a central role in immune regulation in the gut. Toxoplasma gondii is a protozoan intracellular parasite that is usually transmitted through oral infection. Although much of the information on immunity to T. gondii has come from i.p. infection models, more recent studies have revealed the importance of studying immunity following infection through the natural peroral route. Oral infection studies have identified many of the key players in the intestinal response; however, they have relied on responses detected days to weeks following infection. Much less is known about how the gut epithelial layer senses and reacts during initial contact with the pathogen. Given the importance of epithelial cells during pathogen invasion, this study uses an in vitro approach to isolate the key players and examine the early response of intestinal epithelial cells during infection by T. gondii. We show that human intestinal epithelial cells infected with T. gondii elicit rapid MAPK phosphorylation, NF-B nuclear translocation, and secretion of IL-8. Both ERK1/2 activation and IL-8 secretion responses were shown to be MyD88 dependent and TLR2 was identified to be involved in the recognition of the parasite regardless of the parasite genotype. Furthermore, we were able to identify additional T. gondii-regulated genes in the infected cells using a pathway-focused array. Together, our findings suggest that intestinal epithelial cells were able to recognize T. gondii during infection, and the outcome is important for modulating intestinal immune responses.

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¹ Address correspondence and reprint requests to Dr. Cynthia A. Leifer, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853-6401. E-mail address: cal59{at}cornell.edu

² Abbreviations used in this paper: DC, dendritic cell; shRNA, short hairpin RNA; STAg, soluble Toxoplasma Ag; WM, wortmannin; YFP, yellow fluorescent protein.

³ The online version of this article contains supplemental material.