title: BHV-1 infection and inflammatory cytokines amplify the interaction of Mannheimia haemolytica leukotoxin with bovine peripheral blood mononuclear cells in vitro.
abstract: Bovine herpesvirus-1 (BHV-1) has been reported to increase the susceptibility of cattle to respiratory disease caused by Mannheimia (Pasteurella) haemolytica A1. The principal virulence factor of M. haemolytica is a leukotoxin (LKT) that can specifically kill ruminant leukocytes following its binding to the beta2-integrin CD11a/CD18 (lymphocyte function-associated antigen 1 (LFA-1)). In this study, we investigated the effects of experimental infection of bovine peripheral blood mononuclear cells (MNCs) with BHV-1 in vitro, on the subsequent interaction of these cells with the M. haemolytica LKT. We found that BHV-1 infection increased LFA-1 expression (as assessed by flow cytometry), and subsequently enhanced LKT binding and cytotoxicity to bovine MNCs. We also found that BHV-1 infection increased CD18, IL-1beta, and IFN-gamma mRNA expression by MNCs. As previously reported for bovine polymorphonuclear neutrophils (PMNs), MNCs increased their expression of LFA-1, and their LKT binding and cytotoxicity, following exposure to IL-1beta, TNF-alpha, and IFN-gamma. These findings suggest that BHV-1 infection, and the resulting release of inflammatory cytokines, can stimulate expression of LFA-1 in bovine MNCs, thus enhancing the binding and biological effects of LKT. If such a mechanism occurs in vivo it might explain, in part, the increased susceptibility of BHV-1 infected cattle to bovine pasteurellosis.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: F
authors.initials: F
authors.lastname: Leite
authors.forename: C
authors.initials: C
authors.lastname: Kuckleburg
authors.forename: D
authors.initials: D
authors.lastname: Atapattu
authors.forename: R
authors.initials: R
authors.lastname: Schultz
authors.forename: C J
authors.initials: CJ
authors.lastname: Czuprynski
mesh_terms: D000818:Animals; D002417:Cattle; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005098:Exotoxins / Q000276:immunology; D005260:Female; D005434:Flow Cytometry / Q000662:veterinary; D006566:Herpesviridae Infections / Q000276:immunology / Q000382:microbiology / Q000662:veterinary* / Q000821:virology; D007242:Herpesvirus 1, Bovine / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D016978:Mannheimia haemolytica / Q000276:immunology*; D012766:Pasteurellosis, Pneumonic / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary
chemical_list: D016207:Cytokines; D005098:Exotoxins; D016169:Lymphocyte Function-Associated Antigen-1; C018579:leukotoxin; D012313:RNA