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Title: Bovine gamma delta T cells contribute to exacerbated IL-17 production in response to co-infection with Bovine RSV and Mannheimia haemolytica

item MCGILL, JODI - Kansas State University
item RUSK, RACHEL - Kansas State University
item GUERRA-MAUPOME, MARIANA - Kansas State University
item Briggs, Robert
item Sacco, Randy

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/25/2016
Publication Date: 3/4/2016
Citation: McGill, J.L., Rusk, R.A., Guerra-Maupome, M., Briggs, R.E., Sacco, R.E. 2016. Bovine gamma delta T cells contribute to exacerbated IL-17 production in response to co-infection with Bovine RSV and Mannheimia haemolytica. PLoS One. 11(3):e0151083. doi: 10.1371/journal.pone.0151083.

Interpretive Summary: In this manuscript, we have examined the role of a particular protein produced by a specific population of white blood cells in calves in response to a respiratory virus. In addition, we show it is at higher levels during co-infection of this virus with a bacterium. This particular population of white blood cells is found at high levels in the very young calf (up to 60% in some studies). As the calves get older, the percentages of these cells decrease, suggesting they may play an important role in the immune response of the young calf. There have been relatively few studies that have looked at the role of these white blood cells in the immune response to dual infections. The organisms studied are an important cause of respiratory illness in young calves under one year of age and are also an important part of a group of infections that are a leading cause of illness and death in feedlot cattle. This work will be of interest to individuals studying bovine respiratory infections.

Technical Abstract: Human respiratory syncytial virus (HRSV) is a leading cause of severe lower respiratory tract infection in children under five years of age. IL-17 and Th17 responses are increased in children infected with HRSV and have been implicated in both protective and pathogenic roles during infection. Bovine RSV (BRSV) is genetically closely related to HRSV and is a leading cause of severe respiratory infections in young cattle. While BRSV infection in the calf parallels many aspects of human infection with HRSV, IL-17 and Th17 responses have not been studied in the bovine. Here we demonstrate that calves infected with BRSV express significant levels of IL-17, IL-21 and IL-22; and both CD4 T cells and 'd T cells contribute to this response. In addition to causing significant morbidity from uncomplicated infections, BRSV infection also contributes to the development of bovine respiratory disease complex (BRDC), a leading cause of morbidity in both beef and dairy cattle. BRDC is caused by a primary viral infection, followed by secondary bacterial pneumonia by pathogens such as Mannheimia haemolytica. Here, we demonstrate that in vivo infection with M. haemolytica results in increased expression of IL-17, IL-21 and IL-22. We have also developed an in vitro model of BRDC and show that co-infection of PBMC with BRSV followed by M. haemolytica leads to significantly exacerbated IL-17 production, which is primarily mediated by IL-17-producing 'd T cells. Together, our results demonstrate that calves, like humans, mount a robust IL-17 response during RSV infection; and suggest a previously unrecognized role for IL-17 and 'd T cells in the pathogenesis of BRDC.