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肠道沙眼衣原体非致病性定植作为诱导黏膜保护的口服疫苗。

Nonpathogenic Colonization with Chlamydia in the Gastrointestinal Tract as Oral Vaccination for Inducing Transmucosal Protection.

机构信息

The 3rd Xiangya Hospital, Central South University, Changsha, Hunan, China.

Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

出版信息

Infect Immun. 2018 Jan 22;86(2). doi: 10.1128/IAI.00630-17. Print 2018 Feb.

Abstract

has been detected in the gastrointestinal tracts of humans and animals. We now report that gastrointestinal is able to induce robust transmucosal protection in mice. colonization in the gastrointestinal tract correlated with both a shortened course of genital tract infection and stronger protection against subsequent genital tract challenge infection. Mice preinoculated intragastrically with became highly resistant to subsequent infection in the genital tract, resulting in prevention of pathology in the upper genital tract. The transmucosal protection in the genital tract was rapidly induced, durable, and dependent on major histocompatibility complex (MHC) class II antigen presentation but not MHC class I antigen presentation. Although a deficiency in CD4 T cells only partially reduced the transmucosal protection, depletion of CD4 T cells from B cell-deficient mice completely abolished the protection, suggesting a synergistic role of both CD4 T and B cells in the gastrointestinal -induced transmucosal immunity. However, the same protective immunity did not significantly affect colonization in the gastrointestinal tract. The long-lasting colonization with was restricted to the gastrointestinal tract and was nonpathogenic to either gastrointestinal or extragastrointestinal tissues. Furthermore, gastrointestinal did not alter the gut microbiota or the development of gut mucosal resident memory T cell responses to a nonchlamydial infection. Thus, may be developed into a safe and orally deliverable replicating vaccine for inducing transmucosal protection.

摘要

已在人类和动物的胃肠道中检测到。我们现在报告,胃肠道能够诱导小鼠产生强烈的黏膜保护作用。胃肠道中的定植与生殖道感染过程缩短以及对随后的生殖道挑战感染的更强保护作用相关。用预先经胃内接种的 进行预处理的小鼠对随后的生殖道感染具有高度抗性,从而防止上生殖道的病理学发生。生殖道中的黏膜保护作用迅速诱导,持久,并依赖于主要组织相容性复合体(MHC)II 类抗原呈递,但不依赖于 MHC I 类抗原呈递。尽管 CD4 T 细胞缺乏仅部分降低了黏膜保护作用,但从 B 细胞缺陷小鼠中耗尽 CD4 T 细胞则完全消除了保护作用,这表明 CD4 T 和 B 细胞在胃肠道诱导的黏膜免疫中具有协同作用。然而,相同的保护性免疫作用并未显著影响胃肠道中的定植。胃肠道中长时间的 定植仅限于胃肠道,对胃肠道或肠外组织均无致病性。此外,胃肠道 不会改变肠道微生物群或对非衣原体感染的肠道黏膜固有记忆 T 细胞反应的发展。因此,可能将 开发成一种安全的、可口服的复制疫苗,用于诱导黏膜保护作用。

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