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Complexities of the pathogenesis of Mannheimia haemolytica and Haemophilus somnus infections: challenges and potential opportunities for prevention?

Published online by Cambridge University Press:  28 February 2007

Charles J. Czuprynski ,
Fabio Leite ,
Matt Sylte ,
C. Kuckleburg ,
Ron Schultz ,
Tom Inzana ,
Erica Behling-Kelly  and
Lynette Corbeil
Charles J. Czuprynski*
Affiliation:
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI
Fabio Leite
Affiliation:
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI
Matt Sylte
Affiliation:
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI
C. Kuckleburg
Affiliation:
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI
Ron Schultz
Affiliation:
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI
Tom Inzana
Affiliation:
Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA
Erica Behling-Kelly
Affiliation:
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI
Lynette Corbeil
Affiliation:
Department of Pathology, School of Medicine, University of California, San Diego, CA, USA
*
*University of Wisconsin-Madison, School of Veterinary Medicine, 2015 Linden Dr. West, Madison, WI 53706, USA E-mail: CZUPRYNC@SVM.VETMED.WISC.EDU
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Abstract

Progress in producing improved vaccines against bacterial diseases of cattle is limited by an incomplete understanding of the pathogenesis of these agents. Our group has been involved in investigations of two members of the family Pasteurellaceae, Mannheimia haemolytica and Haemophilus somnus, which illustrate some of the complexities that must be confronted. Susceptibility to M. haemolytica is greatly increased during active viral respiratory infection, resulting in rapid onset of a severe and even lethal pleuropneumonia. Despite years of investigation, understanding of the mechanisms underlying this viral–bacterial synergism is incomplete. We have investigated the hypothesis that active viral infection increases the susceptibility of bovine leukocytes to the M. haemolytica leukotoxin by increasing the expression of or activating the β2 integrin CD11a/CD18 (LFA-1) on the leukocyte surface. In vitro exposure to proinflammatory cytokines (i.e. interleukin-1β, tumor necrosis factor-α and interferon-γ) increases LFA-1 expression on bovine leukocytes, which in turn correlates with increased binding and responsiveness to the leukotoxin. Alveolar macrophages and peripheral blood leukocytes from cattle with active bovine herpesvirus-1 (BVH-1) infection are more susceptible to the lethal effects of the leukotoxin ex vivo than leukocytes from uninfected cattle. Likewise, in vitro incubation of bovine leukocytes with bovine herpesvirus 1 (BHV-1) potentiates LFA-1 expression and makes the cells more responsive to leukotoxin. A striking characteristic of H. somnus infection is its propensity to cause vasculitis. We have shown that H. somnus and its lipo-oligosaccharide (LOS) trigger caspase activation and apoptosis in bovine endothelial cells in vitro. This effect is associated with the production of reactive oxygen and nitrogen intermediates, and is amplified in the presence of platelets. The adverse effects of H. somnus LOS are mediated in part by activation of endothelial cell purinergic receptors such as P2X7. Further dissection of the pathways that lead to endothelial cell damage in response to H. somnus might help in the development of new preventive or therapeutic regimens. A more thorough understanding of M. haemolytica and H. somnus virulence factors and their interactions with the host might identify new targets for prevention of bovine respiratory disease.

Keywords

pathogenesisinfectionsMannheimia haemolyticaHaemophilus somnus
Type
Research Article
Information
Animal Health Research Reviews , Volume 5 , Issue 2 , December 2004 , pp. 277 - 282
Copyright
Copyright © CAB International 2004

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