<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>The severity of bovine respiratory infections has been linked to a variety of
factors, including environmental and nutritional changes, transportation, and social
reorganization of weaned calves. Fatal respiratory infections, however, usually occur
when a primary viral infection compromises host defences and enhances the severity
of a secondary bacterial infection. This viral–bacterial synergy can occur by a number
of different mechanisms and disease challenge models have been developed to analyse
host responses during these respiratory infections. A primary bovine herpesvirus-1
(BHV-1) respiratory infection followed by a secondary challenge with <italic>Mannheimia haemolytica</italic>
results in fatal bovine respiratory disease (BRD) and host responses to these 
two pathogens have been studied extensively. We used this disease model to
demonstrate that stress significantly altered the viral–bacterial synergy resulting in
fatal BRD. Functional genomic analysis revealed that BHV-1 infection enhanced toll-like
receptors (TLR) expression and increased pro-inflammatory responses which
contribute to the severity of a <italic>Mannheimia haemolytica</italic> infection. TLRs play a critical
role in detecting bacterial infections and inducing pro-inflammatory responses. It is
difficult to understand, however, how stress-induced corticosteroids could enhance
this form of viral–bacterial synergy. Nuclear translocation of the glucocorticoid
receptor activates cell signalling pathways which inhibit both TLR signalling
and pro-inflammatory responses. The apparent conundrum between stress-induced
corticosteroids and enhanced BRD susceptibility is discussed in terms of present data
and previous investigations of stress and respiratory disease.</p>
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Comp Funct Genomics. 2005 Jun; 6(4):244-250