Opposing effects of acellular and whole cell pertussis vaccines on Bordetella pertussis biofilm formation, Siglec-F+ neutrophil recruitment and bacterial clearance in mouse nasal tissues.
Opposing effects of acellular and whole cell pertussis vaccines on Bordetella pertussis biofilm formation, Siglec-F+ neutrophil recruitment and bacterial clearance in mouse nasal tissues.
复制标题
无细胞和全细胞百日咳疫苗对小鼠鼻组织中百日咳博德特氏菌生物膜形成、Siglec-F 中性粒细胞募集和细菌清除的相反作用。
DOI：
10.1101/2024.01.23.576795
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Dubey,Purnima
中科院分区：
文献类型：
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作者：
Hall,JesseM;Gutiérrez-Ferman,JessicaL;Shamseldin,MohamedM;Guo,Myra;Gupta,YashA;Deora,Rajendar;Dubey,Purnima
尽管全球疫苗接种，百日咳引起的百日咳（Bp）是死灰复燃。百日咳死灰复燃与从引发TH1/TH17极化免疫应答的全细胞疫苗（wPV）转向主要引发TH2极化免疫应答的无细胞百日咳疫苗（aPV）相关。apv免疫个体发病率增加的一种解释是鼻子缺乏细菌清除。为了了解Bp持续存在的宿主和细菌机制，我们评估了naïve和免疫小鼠在Bp攻击后鼻腔相关组织（NT）中的细菌定位和免疫反应。Bp以生物膜的形式存在于未免疫和apv免疫小鼠的NT中。相比之下，wpv免疫小鼠未观察到Bp生物膜。感染后，与aPV免疫小鼠相比，wPV免疫小鼠的鼻部招募了更高水平的siglece - f +中性粒细胞，这是消除鼻部Bp的关键。与这一观察结果一致的是，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局限于NT内，不能通过鼻腔灌洗（NL）恢复。总之，我们的数据表明，由aPV疫苗接种产生的TH2极化免疫反应通过阻止免疫效应物的浸润和生物膜的根除，促进了NT的持续存在。相反，由wPV产生的TH1/TH17免疫表型，招募Siglec-F+中性粒细胞，迅速消除细菌负担并阻止生物膜的建立。因此，我们的工作表明，aPV和wPV对呼吸道Bp生物膜的形成有相反的影响，这为aPV疫苗无法控制鼻内细菌数量和预防传播提供了机制解释。
Despite global vaccination, pertussis caused by Bordetella pertussis (Bp) is resurging. Pertussis resurgence is correlated with the switch from whole cell vaccines (wPV) that elicit TH1/TH17 polarized immune responses to acellular pertussis vaccines (aPV) that elicit primarily TH2 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 Bp persistence, we evaluated bacterial localization and the immune response in the nasal associated tissues (NT) of naïve and immunized mice following Bp challenge. Bp resided in the NT of unimmunized and aPV-immunized mice as biofilms. In contrast, Bp biofilms were not observed in wPV-immunized mice. Following infection, Siglec-F+ neutrophils, critical for eliminating Bp 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 TH2 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 TH1/TH17 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 Bp 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.