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Open Access Research

Stress significantly increases mortality following a secondary bacterial respiratory infection

Paul D Hodgson1, Palok Aich12, Joseph Stookey3, Yurij Popowych1, Andrew Potter1, Lorne Babiuk14 and Philip J Griebel15*

Author Affiliations

1 Vaccine & Infectious Disease Organization, 120 Veterinary Road, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3

2 School of Biological Sciences, National Institute of Science Education and Research (NISER). IOP Campus, Bhubaneswar 751005 Odisha, India

3 WCVM, 52 Campus Drive, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3

4 University of Alberta, Edmonton, AB, Canada

5 School of Public Health, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3

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Veterinary Research 2012, 43:21  doi:10.1186/1297-9716-43-21

Published: 21 March 2012


A variety of mechanisms contribute to the viral-bacterial synergy which results in fatal secondary bacterial respiratory infections. Epidemiological investigations have implicated physical and psychological stressors as factors contributing to the incidence and severity of respiratory infections and psychological stress alters host responses to experimental viral respiratory infections. The effect of stress on secondary bacterial respiratory infections has not, however, been investigated. A natural model of secondary bacterial respiratory infection in naive calves was used to determine if weaning and maternal separation (WMS) significantly altered mortality when compared to calves pre-adapted (PA) to this psychological stressor. Following weaning, calves were challenged with Mannheimia haemolytica four days after a primary bovine herpesvirus-1 (BHV-1) respiratory infection. Mortality doubled in WMS calves when compared to calves pre-adapted to weaning for two weeks prior to the viral respiratory infection. Similar results were observed in two independent experiments and fatal viral-bacterial synergy did not extend beyond the time of viral shedding. Virus shedding did not differ significantly between treatment groups but innate immune responses during viral infection, including IFN-γ secretion, the acute-phase inflammatory response, CD14 expression, and LPS-induced TNFα production, were significantly greater in WMS versus PA calves. These observations demonstrate that weaning and maternal separation at the time of a primary BHV-1 respiratory infection increased innate immune responses that correlated significantly with mortality following a secondary bacterial respiratory infection.