β-Defensins Coordinate In Vivo to Inhibit Bacterial Infections of the Trachea

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.

The influence of insufficiency of vitamin D on activity of endogenous antimicrobic peptides at children of early age with acute bacterial diseases of the respiratory system

“…The obtained data confirm the assumption that vitamin D had influence and on synthesis β1defensins in epithelial cells of respiratory tracts, providing big protection against penetration of pathogenic microflora [13,17,19]. The similar trend was established by us concerning features of providing children with acute bacterial diseases of a respiratory system β1defensins (tab.2).…”

Cytotoxicity of the effector protein BteA was attenuated in Bordetella pertussis by insertion of an alanine residue

“…bronchiseptica inhibits the generation of IFNγ-producing cells and hinders the development of anti- Bordetella serum antibodies [ 16 , 19 ]. Further, T3SS-mediated suppression of the NF -κB pathway activation might downregulate the expression of innate immune genes encoding anti-microbial peptides, and also pro-inflammatory cytokines and chemokines, thereby attenuating recruitment of inflammatory cells to the sites of Bordetella infection [ 16 , 34 , 35 ]. In line with that, we show here that the bteA ΔA503 mutant of B .…”

Porcine Beta-Defensin 2 Provides Protection Against Bacterial Infection by a Direct Bactericidal Activity and Alleviates Inflammation via Interference With the TLR4/NF-κB Pathway

“…Although the expression level of PBD-2 in the TG mice can reach 10 4 ng/g tissue according to our previous study (24), it may be insufficiently high to deal with all the infected bacteria in vivo . Another fact is that some virulence factors and metabolites of bacteria can inhibit the expression of defensins (40, 41). Hence, further increasing the expression level of PBD-2 in vivo , such as by introducing more robust promoter or more copies of PBD-2, might increase the disease resistance abilities of animals.…”