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宿主PTX3蛋白与细菌荚膜在感染过程中协同调节炎症反应。

Host PTX3 Protein and Bacterial Capsule Coordinately Regulate the Inflammatory Response during Infection.

作者信息

Bai Qiankun, Fan Ruhui, Zhong Ningyuan, Liu Jianan, Pan Xinming, Yao Huochun, Ma Jiale

机构信息

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.

Key Laboratory of Animal Bacteriology, Ministry of Agriculture, Nanjing 210095, China.

出版信息

Vet Sci. 2023 Mar 22;10(3):239. doi: 10.3390/vetsci10030239.

Abstract

serotype 2 (SS2) is a noteworthy zoonotic pathogen that has been responsible for large economic losses in pig production and a great threat to human health. Pentraxin 3 (PTX3) is an essential regulator of the innate immune response to bacterial pathogens; however, its role during SS2 infection is not fully understood. In this study, we found that the SS2 strain HA9801 induced a significant inflammatory response in the mouse air pouch model; this response was amplified by the treatment of exogenous PTX3 simultaneously in terms of the results of inflammatory cell recruitment and proinflammatory cytokine IL-6 production. In addition, PTX3 facilitated the phagocytosis of macrophage Ana-1 against SS2 strain HA9801. The supplementation of exogenous PTX3 significantly reduced the bacterial loads in a dose-dependent manner in lungs, livers and bloods of SS2-infected mice compared to the samples with HA9801 infection alone; this finding indicated that PTX3 may facilitate the bacterial clearance through enhancing the host inflammatory response during SS2 infection. Both PTX3 and SS2 capsular polysaccharide (CPS2) were required for the robust inflammatory response, implying that the host PTX3 protein and SS2 surface CPS2 modulate the host innate immune response in concert. All of these results suggested that PTX3 is a potential novel biological agent for the SS2 infection; however, the recommended dose of PTX3 must be evaluated strictly to avoid inducing an excessive inflammatory response that can cause serious tissue injury and animal death.

摘要

2型血清型(SS2)是一种值得关注的人畜共患病原体,它给养猪业造成了巨大经济损失,并对人类健康构成重大威胁。五聚体蛋白3(PTX3)是对细菌病原体先天性免疫反应的重要调节因子;然而,其在SS2感染过程中的作用尚未完全明确。在本研究中,我们发现SS2菌株HA9801在小鼠气袋模型中诱导了显著的炎症反应;从炎症细胞募集和促炎细胞因子IL-6产生的结果来看,同时给予外源性PTX3可增强这种反应。此外,PTX3促进了巨噬细胞Ana-1对SS2菌株HA9801的吞噬作用。与仅感染HA9801的样本相比,补充外源性PTX3以剂量依赖的方式显著降低了SS2感染小鼠肺、肝和血液中的细菌载量;这一发现表明,PTX3可能通过增强SS2感染期间的宿主炎症反应来促进细菌清除。强烈的炎症反应需要PTX3和SS2荚膜多糖(CPS2)共同参与,这意味着宿主PTX3蛋白和SS2表面CPS2协同调节宿主先天性免疫反应。所有这些结果表明,PTX3是一种针对SS2感染的潜在新型生物制剂;然而,必须严格评估PTX3的推荐剂量,以避免诱导过度的炎症反应,从而导致严重的组织损伤和动物死亡。

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