title: Intestinal intraepithelial lymphocytes sustain the epithelial barrier function against Eimeria vermiformis infection.
abstract: 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-gamma) and tumor necrosis factor alpha (TNF-alpha) and decreased transforming growth factor beta (TGF-beta) production. Addition of IFN-gamma and TNF-alpha 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-beta attenuated the damage of epithelial monolayer and changes in TER caused by IFN-gamma and TNF-alpha. The expression of junctional molecules by EC was decreased when IEL produced a high level of IFN-gamma and TNF-alpha and a low level of TGF-beta 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.
authors.affiliation: Parasitic Diseases Unit, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan. INAGAKI@med.miyazaki-u.ac.jp
authors.forename: Kyoko
authors.initials: K
authors.lastname: Inagaki-Ohara
authors.forename: Fitriya Nurannisa
authors.initials: FN
authors.lastname: Dewi
authors.forename: Hajime
authors.initials: H
authors.lastname: Hisaeda
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Smith
authors.forename: Fumiko
authors.initials: F
authors.lastname: Jimi
authors.forename: Maki
authors.initials: M
authors.lastname: Miyahira
authors.forename: Ayman Samir Farid
authors.initials: AS
authors.lastname: Abdel-Aleem
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Horii
authors.forename: Yukifumi
authors.initials: Y
authors.lastname: Nawa
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003048:Coccidiosis / Q000276:immunology*; D004539:Eimeria; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D007421:Intestine, Small / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D062793:Occludin; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000906:Antibodies; D015820:Cadherins; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma