Abstract
Glaesserella parasuis (G. parasuis) is a commensal bacterium in the upper respiratory tract of pigs that can also cause the swine Glässer disease, which induces an intensive inflammatory response and results in significant economic losses to the swine industry worldwide. G. parasuis can cause disease through infection of the respiratory tract, resulting in systemic infection, but the mechanism is largely unknown. Recently we showed that Glaesserella parasuis serotype 4 (GPS4) increased swine tracheal epithelial barrier permeability, resulting in easier bacterial translocation. Tight junction proteins (TJ) play a crucial role in maintaining the integrity and impermeability of the epithelial barrier. GPS4 decreased the expression of the TJ ZO-1 and occludin in swine tracheal epithelial cells (STEC). Furthermore, the proinflammatory cytokines IL-6, IL-8 and TNF-α were significantly upregulated in GPS4-infected STEC, and both the MAPK and NF-κB signaling pathways were activated and contributed to the expression of TNF-α. We demonstrate that the production of proinflammatory cytokines, especially TNF-α, during GPS4 infection was involved in barrier dysfunction. Additionally, animal challenge experiments confirmed that GPS4 infection downregulated TJ in the lungs of piglets and induced a severe inflammatory response. In general, G. parasuis infection downregulated the expression of TJ and induced massive secretion of proinflammatory cytokines, resulting in epithelial barrier disruption and favoring bacterial infection. This study allowed us to better understand the mechanism by which G. parasuis crosses the respiratory tract of pigs.
Highlights
Glaesserella parasuis (G. parasuis), the causative agent of Glässer disease, is a Gram-negative opportunistic bacterial pathogen that colonizes the upper respiratory tract of pigs
Giemsa staining results show that HPS4-YC had a potential to infect swine tracheal epithelial cells (STEC), and that the number of bacteria observed increased with increasing multiplicity of infection (MOI) (Figure 1A)
The results show that there was no significant cytotoxicity to infected cells when the MOI of HPS4-YC were 10 and 100 within 24 h
Summary
Glaesserella parasuis (G. parasuis), the causative agent of Glässer disease, is a Gram-negative opportunistic bacterial pathogen that colonizes the upper respiratory tract of pigs. As a pathogen that can cause infection through the respiratory tract, G. parasuis has to break through the respiratory epithelial barrier to enter the bloodstream and induce systemic infection. Some studies have demonstrated that respiratory pathogens can disrupt epithelial TJ and damage barrier function [10, 11]. Streptococcus pneumoniae and Haemophilus influenzae infection cause downregulation of TJ in human airway epithelial cells and induce disruption of epithelial barrier integrity [11]. There are few studies on the effects of G. parasuis on TJ expression and respiratory epithelial barrier integrity [13, 14]. The aim of the study is to investigate how G. parasuis disrupts the respiratory epithelial barrier to cause systemic infection
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