Abstract
β-defensins are predicted to play an important role in innate immunity against bacterial infections in the airway. We previously observed that a type III-secretion product of Bordetella bronchiseptica inhibits the NF-κB-mediated induction of a β-defensin in airway epithelial cells in vitro. To confirm this in vivo and to examine the relative roles of other β-defensins in the airway, we infected wild-type C57BL/6 mice and mice with a deletion of the mBD-1 gene with B. bronchiseptica wild-type strain, RB50 and its mutant strain lacking the type III-secretion system, WD3. The bacteria were quantified in the trachea and the nasal tissue and mRNA levels of mouse β-defensin-3 (mBD-3) were assessed after 24 h. Infection with the wild-type bacterial strain resulted in lower mBD-3 mRNA levels in the trachea than in mice infected with the type III-deficient strain. Furthermore, we observed an increase in bacterial numbers of RB50 only in the tracheas of mBD-1-deficient mice. Neutrophils were also more abundant on the trachea in RB50 infected WT mice but not in the bronchiolar lavage fluid (BAL), compared with WD3 infected WT and mBD-1−/− mice, indicating that the coordination of β-defensin chemotactic effects may be confined to tracheal epithelial cells (TEC). RB50 decreased the ability of mice to mount an early specific antibody response, seven days after infection in both WT and mBD-1−/− mice but there were no differences in titers between RB50-infected WT and mBD-1−/− mice or between WD3-infected WT and mBD-1−/− mice, indicating mBD-1 was not involved in induction of the humoral immune response to the B. bronchiseptica. Challenge of primary mouse TEC in vitro with RB50 and WD3, along with IL-1β, further corroborated the in vivo studies. The results demonstrate that at least two β-defensins can coordinate early in an infection to limit the growth of bacteria in the trachea.
Highlights
IntroductionBacteria that cause infections in the airway must evade a number of host defense mechanisms that normally combine to prevent these microorganisms from colonization (reviewed in [1,2,3]).One component of this defense is the production of antimicrobial peptides such as β-defensins in the tracheal mucosa, which are either constitutively produced, or induced by cytokines and other bacterial components such as lipopolysaccharide (LPS) via regulation by the transcription factor, NF-κB [4,5,6,7,8].Vaccines 2018, 6, 57; doi:10.3390/vaccines6030057 www.mdpi.com/journal/vaccinesPreviously, several studies have demonstrated that introducing bacterial pathogens can induce gene expression of β-defensins in airway epithelial cells (AEC) both in vitro and in vivo, through activation of innate immune pathways leading to the activation of NF-κB-mediated gene expression [9,10,11,12,13,14,15,16]
Several studies have demonstrated that introducing bacterial pathogens can induce gene expression of β-defensins in airway epithelial cells (AEC) both in vitro and in vivo, through activation of innate immune pathways leading to the activation of NF-κB-mediated gene expression [9,10,11,12,13,14,15,16]
Our research has demonstrated that the active type III secretion system was sufficient to inhibit the bacteria-mediated induction of the bovine homologue to human β-defensin-2, tracheal antimicrobial peptide (TAP), in cultured bovine tracheal epithelial cells (TEC), whereas the WD3 mutant did not inhibit the induction of TAP [12]
Summary
Bacteria that cause infections in the airway must evade a number of host defense mechanisms that normally combine to prevent these microorganisms from colonization (reviewed in [1,2,3]).One component of this defense is the production of antimicrobial peptides such as β-defensins in the tracheal mucosa, which are either constitutively produced, or induced by cytokines and other bacterial components such as lipopolysaccharide (LPS) via regulation by the transcription factor, NF-κB [4,5,6,7,8].Vaccines 2018, 6, 57; doi:10.3390/vaccines6030057 www.mdpi.com/journal/vaccinesPreviously, several studies have demonstrated that introducing bacterial pathogens can induce gene expression of β-defensins in airway epithelial cells (AEC) both in vitro and in vivo, through activation of innate immune pathways leading to the activation of NF-κB-mediated gene expression [9,10,11,12,13,14,15,16]. Bacteria that cause infections in the airway must evade a number of host defense mechanisms that normally combine to prevent these microorganisms from colonization (reviewed in [1,2,3]). One component of this defense is the production of antimicrobial peptides such as β-defensins in the tracheal mucosa, which are either constitutively produced, or induced by cytokines and other bacterial components such as lipopolysaccharide (LPS) via regulation by the transcription factor, NF-κB [4,5,6,7,8]. To support the hypothesis that β-defensins are important in airway defense in vivo, two studies showed some delayed clearance of Haemophilus influenzae [21] and no significant effect on infection of Staphylococcus aureus and Streptococcus pneumoniae [22] in mice lacking mouse β-defensin-1 (mBD-1).
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