Intestinal intraepithelial lymphocytes sustain the epithelial barrier function against Eimeria vermiformis infection
Intestinal intraepithelial lymphocytes sustain the epithelial barrier function against Eimeria vermiformis infection
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DOI：
10.1128/iai.02024-05
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发表时间：
2006-09-01
影响因子：
3.1
通讯作者：
Nawa, Yukifumi
中科院分区：
文献类型：
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作者：
Inagaki-Ohara, Kyoko;Dewi, Fitriya Nurannisa;Nawa, Yukifumi
艾美耳球虫属是细胞内的原生动物，感染大多数脊椎动物的肠上皮，引起球虫病。肠上皮内淋巴细胞（IEL）位于上皮细胞（EC）的基底外侧部位，对艾美耳球虫具有免疫调节和免疫保护作用。感染然而，在艾美耳球虫感染过程中，IEL如何参与上皮屏障的调节仍然是未知的。在这里，我们证明了两个不同的作用IEL对感染蠕虫状艾美耳球虫，鼠病原体：生产细胞因子诱导保护性免疫和表达的连接分子，以保持上皮屏障。当卵囊产量达到高峰时，IEL的数量显著增加。在感染期间，IEL增加γ干扰素（IFN-γ）和肿瘤坏死因子α（TNF-α）的产生，并减少转化生长因子β（TGF-β）的产生。加入IFN-γ和TNF-α或从E.蠕虫感染的小鼠降低了融合的CMT 93细胞单层（一种鼠源性上皮细胞系）的跨上皮电阻（TER），但针对这些细胞因子的抗体抑制了TER的下降。此外，TGF-β减弱了由IFN-γ和TNF-α引起的上皮单层损伤和TER变化。当IEL产生高水平的IFN-γ和TNF-α而低水平的TGF-β时，EC的连接分子表达减少。蠕虫感染的小鼠。有趣的是，IEL不断表达连接分子和EC与IEL的共培养增加TER。这些结果表明，IEL不仅在保护上皮细胞免受E.蠕虫引起的细胞因子产生的变化，但也在直接与上皮屏障时，EC内连接下调相互作用。
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.