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Infection and Immunity, September 2006, p. 5292-5301, Vol. 74, No. 9
0019-9567/06/$08.00+0 doi:10.1128/IAI.02024-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Intestinal Intraepithelial Lymphocytes Sustain the Epithelial Barrier Function against Eimeria vermiformis Infection
Kyoko Inagaki-Ohara,1* Fitriya Nurannisa Dewi,2,3 Hajime Hisaeda,4 Adrian L. Smith,5 Fumiko Jimi,2 Maki Miyahira,2 Ayman Samir Farid Abdel-Aleem,2 Yoichiro Horii,2 and Yukifumi Nawa1Parasitic Diseases Unit, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan,1 Department of Veterinary Teaching Hospital and Internal Medicine, Faculty of Agriculture, University of Miyazaki, Gakuen Kibanadai Nishi, Miyazaki 889-2192, Japan,2 Faculty of Veterinary Medicine, Bogor Agricultural University, Jalan Agatis Campus IPB Darmaga Bogor 16680, Jawa Barat, Indonesia,3 Department of Parasitology, Graduate School of Medical Science, Kyushu University, 3-1-1 Higashi-ku, Maidashi, Fukuoka 812-8582, Japan,4 Division of Immunology, Institute for Animal Health, Compton, Nr. Newbury, Berkshire RG20 7NN, United Kingdom5
Received 16 December 2005/ Returned for modification 1 March 2006/ Accepted 30 June 2006
Eimeria spp. are intracellular protozoa that infect intestinal epithelia of most vertebrates, causing coccidiosis. Intestinal intraepithelial lymphocytes (IEL) that reside at the basolateral site of epithelial cells (EC) have immunoregulatory and immunoprotective roles against Eimeria spp. infection. However, it remains unknown how IEL are involved in the regulation of epithelial barrier during Eimeria sp. infection. Here, we demonstrated two distinct roles of IEL against infection with Eimeria vermiformis, a murine pathogen: production of cytokines to induce protective immunity and expression of junctional molecules to preserve epithelial barrier. The number of IEL markedly increased when oocyst production reached a peak. During infection, IEL increased production of gamma interferon (IFN-
) and tumor necrosis factor alpha (TNF-
) and decreased transforming growth factor ß (TGF-ß) production. Addition of IFN- and TNF- or supernatants obtained from cultured IEL from E. vermiformis-infected mice reduced transepithelial electrical resistance (TER) in a confluent CMT93 cell monolayer, a murine intestine-derived epithelial line, but antibodies against these cytokines suppressed the decline of TER. Moreover, TGF-ß attenuated the damage of epithelial monolayer and changes in TER caused by IFN- and TNF-. The expression of junctional molecules by EC was decreased when IEL produced a high level of IFN- and TNF- and a low level of TGF-ß in E. vermiformis-infected mice. Interestingly, IEL constantly expressed junctional molecules and a coculture of EC with IEL increased TER. These results suggest that IEL play important multifunctional roles not only in protection of the epithelium against E. vermiformis-induced change by cytokine production but also in direct interaction with the epithelial barrier when intra-EC junctions are down-regulated.
* Corresponding author. Mailing address: Parasitic Diseases Unit, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan. Phone: 81-985-85-0990. Fax: 81-985-84-3887. E-mail: INAGAKI{at}med.miyazaki-u.ac.jp.
Infection and Immunity, September 2006, p. 5292-5301, Vol. 74, No. 9
0019-9567/06/$08.00+0 doi:10.1128/IAI.02024-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
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