The Host Defense Peptide Beta-Defensin 1 Confers Protection against Bordetella pertussis in Newborn Piglets

Abstract

Innate immunity plays an important role in protection against respiratory infections in humans and animals. Host defense peptides such as beta-defensins represent major components of innate immunity. We recently developed a novel porcine model of pertussis, an important respiratory disease of young children and infants worldwide. Here, we investigated the role of porcine beta-defensin 1 (pBD-1), a porcine defensin homologue of human beta-defensin 2, in conferring protection against respiratory infection with Bordetella pertussis. In this model, newborn piglets were fully susceptible to infection and developed severe bronchopneumonia. In contrast, piglets older than 4 weeks of age were protected against infection with B. pertussis. Protection was associated with the expression of pBD-1 in the upper respiratory tract. In fact, pBD-1 expression was developmentally regulated, and the absence of pBD-1 was thought to contribute to the increased susceptibility of newborn piglets to infection with B. pertussis. Bronchoalveolar lavage specimens collected from older animals as well as chemically synthesized pBD-1 displayed strong antimicrobial activity against B. pertussis in vitro. Furthermore, in vivo treatment of newborn piglets with only 500 g pBD-1 at the time of challenge conferred protection against infection with B. pertussis. Interestingly, pBD-1 displayed no bactericidal activity in vitro against Bordetella bronchiseptica, a closely related natural pathogen of pigs. Our results demonstrate that host defense peptides play an important role in protection against pertussis and are essential in modulating innate immune responses against respiratory infections.

Protective Role of Passively Transferred Maternal Cytokines against Bordetella pertussis Infection in Newborn Piglets

“…(iii) Active immunization does not provide protection against infection with B. pertussis in newborn piglets. Piglets of both vaccinated and control groups were challenged with 2 ϫ 10 10 to 5 ϫ 10 10 CFU of live bacteria at 24 to 26 days of age as we described elsewhere (46)(47)(48). Piglets from either control or vaccinated groups displayed clinical symptoms, including mild fever, nasal discharge, nonparoxysmal cough, and breathing difficulties, as we previously showed (46,48).…”

“…Piglets were anesthetized with isoflurane and intubated using a laryngoscope and an endotracheal tube, and bacteria (5 ϫ 10 9 CFU) were delivered through the tube at a level of 1.5 ml/lung craniodorsal to the bronchial bifurcation, as we have previously described elsewhere (44,46,47).…”

Differential antimicrobial peptide gene expression patterns during early chicken embryological development

“…A recent study has shown expression of porcine b-defensin 1 was only present in tongue of newborn piglets, as distinct from a wider panel of tissues in 4-5-week-old pigs [41] . It was therefore o nterest to examine the correlation between this early localisation of b-defensin expression during embryogenesis and the tissue specific expression patterns observed in earlier studies [42,43] .…”

Resurgence of pertussis calls for re-evaluation of pertussis animal models

“…Also, all experimental animal species will have lifespan restrictions when testing durability of protection. Moreover, no model, not even the human, has disclosed a defined correlate or surrogate of protection for pertussis (Table 1) [12,18,22,[96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113].…”