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December 2023

Bordetella spp. block eosinophil recruitment to suppress the generation of early mucosal protection

First NJ, Parrish KM, Martínez-Pérez A et al

Cell Reports 2023; Vol 42, Issue 11 (28 November)

https://doi.org/10.1016/j.celrep.2023.113294

Reviewed by Rachael FitzPatrick, PhD Candidate, Reynolds Laboratory at the University of Victoria, Canada

Bordetella bronchiseptica is a natural murine pathogen in the same bacterial group as the causative agent of whooping cough in humans. Bordetella species have evolved mechanisms to suppress host immune responses and previous work found that a sigma factor expressed by B. bronchiseptica called BtrS is essential for the suppression of eosinophils during Bordetella infection in the murine lung (Gestal MC, et al. Microorganisms. 2020 Nov 17;8(11):1808.). Building on their previous findings, this study characterizes the role of eosinophils during Bordetella infection using a BtrS-null strain of the bacteria where eosinophils are not suppressed and instead are responsive to and even required for the clearance of this bacterial pathogen. This unique infection model offered a clear example of the capacity of eosinophils to facilitate Th1, Th17 and B cell responses to bacterial infection in the lung. 

This has implications for treatment and vaccine development strategies against Bordetella and similar mucosal pathogens. Further translational significance of this work lies in the ability of wild-type B. bronchiseptica to suppress eosinophils via BtrS. BtrS, however, is part of a complex regulatory network not fully understood and the exact mechanism by which BtrS contributes to eosinophil suppression by Bordetella remains to be elucidated. The answer to this outstanding question could inform therapeutic strategies for the treatment of eosinophilic disease states.  

Together, this work contributes to the growing body of evidence showing that eosinophils are highly responsive to bacterial stimuli. It also highlights that the role of eosinophils during bacterial infection is dependent on the infection site, time-course and the bacterial pathogen being investigated. Finally, this study offers an exciting perspective of exploiting evolved mechanisms of bacterial pathogenesis to inform therapeutic strategies for eosinophilic diseases.

Rachael FitzPatrick is a PhD candidate in the Reynolds Laboratory at the University of Victoria, Canada. Rachael began studying eosinophils as an undergraduate and was inspired to continue her research as a graduate student after attending the IES Biennial Symposium in 2019. Rachael has published work on the homeostatic function of eosinophils in the intestinal tract and is now investigating the role of eosinophils during enteric bacterial infection. Outside of the lab Rachael can be found exploring the wet west coast of British Columbia with her toddler. Rachael is serving on the IES Early Career Committee.

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