Bovine respiratory disease (BRD) involves complex interactions amongst viral and bacterial pathogens that can lead to intense pulmonary inflammation (fibrinous pleuropneumoniae). Charles J. Czuprynski, PhD, University Wisconsin-Madison, says viral infection greatly increases the susceptibility of cattle to secondary infection of the lung with bacterial pathogens like Mannheimia haemolytica and Histophilus somnii.
The underlying reason for this viral/bacterial synergism, and the manner in which cattle respond to the virulence strategies of the bacterial pathogens, is incompletely understood. The challenge for the animal is to initiate an innate immune response that overcomes the virulence mechanisms utilized by the viral and bacterial pathogens without eliciting extensive inflammation that can compromise lung function and lead to decreased weight gain.
“Our lab is investigating the participation of respiratory epithelial cells in this process,” Czuprynski says. “Bovine herpesvirus type 1 (BHV-1) infection of bronchial epithelial cells in vitro enhances the binding of M. haemolytica, and triggers release of inflammatory mediators that attract and enhance binding of neutrophils. An exotoxin (leukotoxin) released from M. haemolytica further stimulates release of inflammatory mediators and causes leukocyte death.”
Cattle infected with H. somnii frequently display vasculitis. “We find that exposure of bovine endothelial cells to H. somnii or its lipooligosaccharide (LOS) increases endothelium permeability, and makes the surface of the endothelial cells pro-coagulant,” Czuprynski says. “These processes are amplified in the presence of platelets. The findings demonstrate that bovine respiratory pathogens (BHV-1, M. haemolytica, H. somnii) interact with leukocytes and other cells (epithelial and endothelial cells) leading to the inflammation that characterizes BRD.”
The ability of M. haemolytica to circumvent leukocyte antibacterial activity via its leukotoxin, and H. somnii to resist leukocyte killing while creating a pro-inflammatory and pro-coagulative environment on the endothelial cell surface, likely contributes to the intense inflammation that characterizes BRD. “Efforts to reduce the severity of BRD through vaccination must take these events into account and strive to eliminate the bacterial cells without further exacerbating pulmonary inflammation,” says Czuprynski.