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Mucosal immunity: an overview and studies of enteric and respiratory coronavirus infections in a swine model of enteric disease

机译:粘膜免疫:猪肠道疾病模型中肠道和呼吸冠状病毒感染的概述和研究

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摘要

Based on the tenet of a common mucosal immune system, antigenic stimulation at one mucosal site results in the distribution of antigen-specific IgA precursor cells to distant mucosal sites. However, recent studies suggest that functional compartmentalization and limited reciprocity may exist within some components of the common mucosal immune system. Although oral immunization is often very effective in inducing immunity to respiratory pathogens, the converse (respiratory immunization to prevent enteric diseases) may not be as effective. To address this question and to study interactions between the bronchus-associated (BALT) and gut-associated (GALT) lymphoid tissues related to protective immunity, we used as a model two antigenically related porcine coronaviruses which replicate primarily in the intestine (transmissible gastroenteritis virus, TGEV) or respiratory tract (porcine respiratory coronavirus, PRCV). The tissue distribution and magnitude of the antibody secreting cell (ASC) responses (measured by ELISPOT) and cell-mediated immune responses (measured by lymphoproliferative assays, LPA) coincided with the viral tissue tropisms. Immunization via GALT (gut infection with TGEV) elicited high numbers of IgA ASC and high LPA responses in GALT (gut lamina propria, LP or mesenteric lymph nodes, MLN), but lower responses in BALT (bronchial lymph nodes, BLN) and induced complete protection against enteric TGEV challenge. In contrast immunization via BALT (respiratory infection with PRCV) elicited systemic type responses (high numbers of IgG ASC in the BLN), but few ASC and low LPA responses in the gut LP or MLN and induced only partial protection against enteric TGEV challenge. Thus administration of vaccines intranasally may not be optimally effective for inducing intestinal immunity in contrast to the reported efficacy of oral vaccines for inducing respiratory immunity.
机译:基于常见粘膜免疫系统的宗旨,在一个粘膜部位的抗原刺激导致抗原特异性IgA前体细胞分布到遥远的粘膜部位。但是,最近的研究表明,功能性区室化和有限的互惠性可能存在于普通粘膜免疫系统的某些组件中。尽管口服免疫通常在诱导针对呼吸道病原体的免疫方面非常有效,但相反(预防肠道疾病的呼吸道免疫)可能效果不佳。为了解决这个问题并研究支气管相关(BALT)和肠道相关(GALT)淋巴样组织之间与保护性免疫相关的相互作用,我们以两种抗原相关的猪冠状病毒为模型,它们主要在肠内复制(可传播的胃肠炎病毒)。 ,TGEV)或呼吸道(猪呼吸道冠状病毒,PRCV)。抗体分泌细胞(ASC)反应(通过ELISPOT测量)和细胞介导的免疫反应(通过淋巴增生测定,LPA测量)的组织分布和大小与病毒组织的向性相吻合。通过GALT免疫(肠道病毒用TGEV感染)在GALT(肠道固有层,LP或肠系膜淋巴结,MLN)中引起大量IgA ASC和高LPA反应,而在BALT(支气管淋巴结,BLN)中产生较低的免疫应答并诱导完全防止肠TGEV挑战。相比之下,通过BALT(PRC的呼吸道感染)进行的免疫接种会引起系统性类型应答(BLN中的IgG ASC数量较高),但是在肠道LP或MLN中几乎没有ASC和LPA应答较低,并且仅诱导了针对肠道TGEV攻击的部分保护。因此,与报道的口服疫苗诱导呼吸道免疫的功效相反,鼻内施用疫苗可能不是最佳的诱导肠道免疫的有效药物。

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