Abstract
Bacterial pneumonia causes significant economic loss to the beef industry and occurs at times of stress and viral infection. Administering antibiotics to at-risk calves is often used to prevent the disease, but alternatives to mass treatment with antibiotics are needed. Tracheal antimicrobial peptide (TAP), a β-defensin naturally produced by bovine airways, has bactericidal activity against the pathogens that cause pneumonia in cattle. However, TAP expression is suppressed by glucocorticoid (stress) and viral infection. We hypothesized that delivering TAP to the respiratory tract would prevent development of pneumonia in calves infected with Mannheimia haemolytica. Clean-catch calves (i.e. obtained prior to contact with the dam) were challenged by aerosol with M. haemolytica, and TAP or water was delivered to the respiratory tract at 0.3, 2 and 6 hours post-infection. TAP treatment did not protect against development of disease. Calves treated with TAP had similar bacterial loads in the nasal cavity and lung compared to calves treated with water. Similarly, TAP treatment did not affect the development of clinical signs, elevated rectal temperatures, or increased levels of blood neutrophils, haptoglobin and fibrinogen that occurred after bacterial challenge. Postmortem gross and histologic lung lesions were also similar in the two groups. To determine why there was a lack of protective effect, we tested the effect of substances in respiratory lining fluid on the bactericidal activity of TAP. Physiologic concentrations of sodium chloride inhibited TAP bactericidal activity in vitro, as did serum at concentrations of 0.62 to 2.5%, but concentrated bronchoalveolar lavage fluid had no consistent effect. These findings suggest that TAP does not have in vivo bactericidal activity against M. haemolytica because of interference by physiological sodium chloride levels and by serum. Thus, administration of TAP may not be effective for prevention of M. haemolytica pneumonia.
Highlights
Bovine respiratory disease (BRD) is the most economically important disease affecting production in the beef industry
We have shown that well-recognized factors predisposing cattle to bacterial pneumonia, including stress and viral infection, interfere with the inducible expression of tracheal antimicrobial peptide (TAP), a βdefensin secreted by airway epithelial cells [1,2]
At concentrations of 3.12 and 6.25 μg/mL, non-oxidized TAP killed 96% and 99% of bacteria compared with 17% and 86% killing by oxidized TAP, respectively
Summary
Bovine respiratory disease (BRD) is the most economically important disease affecting production in the beef industry. We have shown that well-recognized factors predisposing cattle to bacterial pneumonia, including stress (modeled by glucocorticoids) and viral infection ( bovine viral diarrhea virus, BVDV), interfere with the inducible expression of tracheal antimicrobial peptide (TAP), a βdefensin secreted by airway epithelial cells [1,2]. Together, these findings suggest that stress and viral infection may impair innate pulmonary defences by modulating the expression of epithelial antimicrobial peptides such as TAP. Other immune defences may be suppressed in stressed and virus-infected beef calves, the susceptibility of BRD pathogens to TAP suggests that restoring expression of this antimicrobial peptide may be an approach to preventing bacterial pneumonia. To investigate possible explanations for the in vivo results, the effect of serum, sodium chloride and bronchoalveolar lavage fluid on in vitro antibacterial activity of TAP was studied
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