Bordetella pseudohinzii targets cilia and impairs tracheal cilia-driven transport in naturally acquired infection in mice

Abstract

Several species of the Gram-negative genus Bordetella are the cause of respiratory infections in mammals and birds, including whooping cough (pertussis) in humans. Very recently, a novel atypical species, Bordetella pseudohinzii, was isolated from laboratory mice. These mice presented no obvious clinical symptoms but elevated numbers of neutrophils in bronchoalveolar lavage fluid and inflammatory signs in histopathology. We noted that this species can occur at high prevalence in a mouse facility despite regular pathogen testing according to the FELASA-recommendations. Affected C57BL/6 J mice had, in addition to the reported pulmonary alterations, tracheal inflammation with reduced numbers of ciliated cells, slower ciliary beat frequency, and largely (>50%) compromised cilia-driven particle transport speed on the mucosal surface, a primary innate defence mechanism. In an in vitro-model, Bordetella pseudohinzii attached to respiratory kinocilia, impaired ciliary function within 4 h and caused epithelial damage within 24 h. Regular testing for this ciliotropic Bordetella species and excluding it from colonies that provide mice for lung research shall be recommended. On the other hand, controlled colonization and infection with Bordetella pseudohinzii may serve as an experimental model to investigate mechanisms of mucociliary clearance and microbial strategies to escape from this primary innate defence response.

Isolation and characterization of Bordetella pseudohinzii in mice in China

“…The bacteria could also be detected in the nasal swabs and lung on days 12 PI, as well as in the trachea and cecal contents. The replication of B. pseudohinzii in trachea and lung of the mice has been demonstrated in previous studies . Our novel finding in the present study was that the infected mice shed the bacteria in their feces which contaminated the cage padding.…”

“…The 16S rRNA gene was amplified using universal primers (forward primer: 5'‐AGAGTTTGATCMTGGCTCAG‐3', reverse primer: 5'‐TACGGYTACCTTGTTACGACTT‐3'). The partial B. pseudohinzii outer membrane protein A (OmpA) gene was amplified using primer pairs as previously described . All the primers were synthesized by Sangon Biotech.…”

“…B. pertussis , the agent of whooping cough in humans, together with B. parapertussis and B. bronchiseptica , are commonly classified as “classical” Bordetella . The other six species ( Bordetella holmesii , Bordetella trematum , Bordetella avium , Bordetella petrii , Bordetella hinzii and Bordetella pseudohinzii ) are classified as “non‐classical” Bordetella …”

“…B. pseudohinzii has been detected and isolated in laboratory mice facilities across the world, including the United States, Japan, Malaysia and Germany . This pathogen will cause immunocompetent mice to have a subclinical infection and immunodeficient mice to have rhinitis or pneumonia respiratory symptoms.…”

Airway Microbiota-Host Interactions Regulate Secretory Leukocyte Protease Inhibitor Levels and Influence Allergic Airway Inflammation

“…Although Bph persists in the respiratory tract of mice for months after inoculation ( Dewan et al, 2019 ), the preponderance of infections do not lead to overt signs of illness ( Hayashimoto et al, 2012 ). Others have reported that despite its apparent benign effects on mice, Bph can induce changes in pulmonary immune parameters (e.g., neutrophilia), leading to concerns about Bph possibly confounding murine pulmonary disease models ( Clark et al, 2016 , 2017 ; Perniss et al, 2018 ). On the other hand, we speculated that studying a bacterium within the context of AAI that evolved to reside in the murine respiratory tract and was not transplanted from humans may provide unique insights into how prolonged exposure to a respiratory microbe affects pulmonary inflammation.…”