Infection of bovine well-differentiated airway epithelial cells by Pasteurella multocida : actions and counteractions in
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RESEARCH ARTICLE
Open Access
Infection of bovine well‑differentiated airway epithelial cells by Pasteurella multocida: actions and counteractions in the bacteria–host interactions Ang Su1†, Jie Tong4†, Yuguang Fu3, Sandy Müller2, Yenehiwot Berhanu Weldearegay2, Paul Becher1, Peter Valentin‑Weigand2, Jochen Meens2* and Georg Herrler1*
Abstract Pasteurella (P.) multocida is a zoonotic pathogen, which is able to cause respiratory disorder in different hosts. In cattle, P. multocida is an important microorganism involved in the bovine respiratory disease complex (BRDC) with a huge economic impact. We applied air–liquid interface (ALI) cultures of well-differentiated bovine airway epithelial cells to analyze the interaction of P. multocida with its host target cells. The bacterial pathogen grew readily on the ALI cultures. Infection resulted in a substantial loss of ciliated cells. Nevertheless, the epithelial cell layer maintained its barrier function as indicated by the transepithelial electrical resistance and the inability of dextran to get from the api‑ cal to the basolateral compartment via the paracellular route. Analysis by confocal immunofluorescence microscopy confirmed the intactness of the epithelial cell layer though it was not as thick as the uninfected control cells. Finally, we chose the bacterial neuraminidase to show that our infection model is a sustainable tool to analyze virulence factors of P. multocida. Furthermore, we provide an explanation, why this microorganism usually is a commensal and becomes pathogenic only in combination with other factors such as co-infecting microorganisms. Keywords: Pasteurella multocida, air–liquid interface (ALI) cultures, bacterial pathogenesis, host–pathogen interactions Introduction Bovine respiratory disease is a multifactorial disease complex of cattle (BRDC) [1–3]. Pasteurella multocida is one of the most important bacterial pathogens related to BRDC [3–5]. With its broad host range comprising humans, domestic animals and wild animals [1, 6, 7], *Correspondence: Jochen.Meens@tiho‑hannover.de; Georg. Herrler@tiho‑hannover.de † Ang Su and Jie Tong contributed equally to this work 1 Institute of Virology, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany 2 Institute of Microbiology, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany Full list of author information is available at the end of the article
P. multocida is considered as one of the most prevalent commensals and opportunistic pathogens worldwide [7, 8]. As a commensal of cattle, P. multocida is located in the upper respiratory tract [1, 9–11]; the pathogenesis of the respiratory disease and the interactions with other respiratory pathogens are largely unknown. Several bacterial components have been identified as virulence factors, e.g. the capsule, lipopolysaccharides, and the neuraminidase (sialidase) [8, 12–17]. A neuraminidase is found in most P. multocida strains [14, 18]. By releasing sialic acid from glycosylated host proteins and lipi
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