Role of Neutrophils in Response toBordetella pertussisInfection in Mice

Abstract

Pertussis is an acute respiratory disease caused by the bacterium Bordetella pertussis, for which humans are the only known reservoir. During infection, B. pertussis releases several toxins, including pertussis toxin (PT) and adenylate cyclase toxin (ACT), which have both been shown to play roles in promoting bacterial growth during early infection in a mouse model. Furthermore, in vitro and in vivo studies suggest that PT and ACT affect neutrophil chemotaxis and/or function, thereby altering the innate immune response. In this study we depleted animals of neutrophils to investigate whether neutrophils play a protective role during B. pertussis infection in mice. In addition, by infection with toxin-deficient strains, we investigated whether neutrophils are the main targets for PT and/or ACT activity in promoting bacterial growth. Surprisingly, we found no role for neutrophils during B. pertussis infection in naïve mice. However, in previously infected (immune) mice or in mice receiving immune serum, we observed a significant role for neutrophils during infection. Furthermore, in this immune mouse model our evidence indicates that neutrophils appear to be the main target cells for ACT, but not for PT.

Cyclic AMP-Mediated Suppression of Neutrophil Extracellular Trap Formation and Apoptosis by the Bordetella pertussis Adenylate Cyclase Toxin

“…Andreasen et al have found that ACT suppresses the neutrophil-mediated clearance of B. pertussis from mice with prior immunity to B. pertussis (68). In addition, ACT expression results in massive neutrophilic infiltration into the lungs of Bordetella bronchiseptica-infected mice (69).…”

Structure and function of RTX toxins

“…Harvill and colleagues [291], by using a murine model of infection, have identified neutrophils and macrophages (that express CD11b/CD18) as the primary targets of the CyaA toxin from B. bronchiseptica, a related animal pathogen. The CyaA toxin, therefore, may represent an essential mechanism of defense against the early steps of innate immune responses [278,292]. CyaA inhibits the phagocytic functions of neutrophils and macrophages by impairing chemotaxis and oxidative response, and eventually triggers cell apoptosis [161,276,284,[293][294][295][296][297][298].…”

Blocking neutrophil diapedesis prevents hemorrhage during thrombocytopenia

“…4). In addition, interference with G i signaling in neu trophils (a process known to be critical for neutrophil trans migration [Skokowa et al, 2005;Wiege et al, 2013]) by PTX treatment (Burns, 1988;Andreasen and Carbonetti, 2009;Bestebroer et al, 2010) or gene ablation (Rudolph et al, 1995) protected thrombocytopenic animals from neutrophil transmi gration and cutaneous hemorrhage (Fig. 6).…”