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无细胞百日咳疫苗和全细胞百日咳疫苗对小鼠鼻组织生物膜形成、Siglec-F⁺中性粒细胞募集及细菌清除的相反作用

Opposing effects of acellular and whole cell pertussis vaccines on biofilm formation, Siglec-F+ neutrophil recruitment and bacterial clearance in mouse nasal tissues.

作者信息

Hall Jesse M, Gutiérrez-Ferman Jessica L, Shamseldin Mohamed M, Guo Myra, Gupta Yash A, Deora Rajendar, Dubey Purnima

机构信息

Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH.

Department of Microbiology, The Ohio State University, Columbus, OH.

出版信息

bioRxiv. 2024 Jan 25:2024.01.23.576795. doi: 10.1101/2024.01.23.576795.

Abstract

Despite global vaccination, pertussis caused by () is resurging. Pertussis resurgence is correlated with the switch from whole cell vaccines (wPV) that elicit T1/T17 polarized immune responses to acellular pertussis vaccines (aPV) that elicit primarily T2 polarized immune responses. One explanation for the increased incidence in aPV-immunized individuals is the lack of bacterial clearance from the nose. To understand the host and bacterial mechanisms that contribute to persistence, we evaluated bacterial localization and the immune response in the nasal associated tissues (NT) of naïve and immunized mice following challenge. resided in the NT of unimmunized and aPV-immunized mice as biofilms. In contrast, biofilms were not observed in wPV-immunized mice. Following infection, Siglec-F+ neutrophils, critical for eliminating from the nose, were recruited to the nose at higher levels in wPV immunized mice compared to aPV immunized mice. Consistent with this observation, the neutrophil chemokine CXCL1 was only detected in the NT of wPV immunized mice. Importantly, the bacteria and immune cells were primarily localized within the NT and were not recovered by nasal lavage (NL). Together, our data suggest that the T2 polarized immune response generated by aPV vaccination facilitates persistence in the NT by impeding the infiltration of immune effectors and the eradication of biofilms In contrast, the T1/T17 immune phenotype generated by wPV, recruits Siglec-F+ neutrophils that rapidly eliminate the bacterial burden and prevent biofilm establishment. Thus, our work shows that aPV and wPV have opposing effects on biofilm formation in the respiratory tract and provides a mechanistic explanation for the inability of aPV vaccination to control bacterial numbers in the nose and prevent transmission.

摘要

尽管进行了全球疫苗接种,但由()引起的百日咳仍在卷土重来。百日咳的复发与疫苗接种从能引发T1/T17极化免疫反应的全细胞疫苗(wPV)转向主要引发T2极化免疫反应的无细胞百日咳疫苗(aPV)有关。aPV免疫个体发病率增加的一个原因是鼻腔中细菌清除不足。为了了解导致(细菌名称缺失)持续存在的宿主和细菌机制,我们评估了初次免疫和再次免疫小鼠在(细菌名称缺失)攻击后鼻相关组织(NT)中的细菌定位和免疫反应。(细菌名称缺失)以生物膜形式存在于未免疫和aPV免疫小鼠的NT中。相比之下,在wPV免疫小鼠中未观察到生物膜。感染后,对于从鼻腔清除(细菌名称缺失)至关重要的Siglec-F+中性粒细胞,在wPV免疫小鼠中被招募到鼻腔的水平高于aPV免疫小鼠。与这一观察结果一致,中性粒细胞趋化因子CXCL1仅在wPV免疫小鼠的NT中检测到。重要的是,细菌和免疫细胞主要定位于NT内,通过鼻腔灌洗(NL)无法回收。总之,我们的数据表明,aPV疫苗接种产生的T2极化免疫反应通过阻碍免疫效应器的浸润和生物膜的根除,促进了(细菌名称缺失)在NT中的持续存在。相比之下,wPV产生的T1/T17免疫表型招募Siglec-F+中性粒细胞,迅速消除细菌负荷并防止生物膜形成。因此,我们的研究表明,aPV和wPV对呼吸道中(细菌名称缺失)生物膜形成具有相反的影响,并为aPV疫苗接种无法控制鼻腔中的细菌数量和预防传播提供了一个机制解释。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c36/10849580/ba7ef00083ae/nihpp-2024.01.23.576795v1-f0001.jpg

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