title: Pathogenic mechanisms implicated in the intravascular coagulation in the lungs of BVDV-infected calves challenged with BHV-1.
abstract: Resistance to respiratory disease in cattle requires host defense mechanisms that protect against pathogens which have evolved sophisticated strategies to evade them, including an altered function of pulmonary macrophages (MΦs) or the induction of inflammatory responses that cause lung injury and sepsis. The aim of this study was to clarify the mechanisms responsible for vascular changes occurring in the lungs of calves infected with bovine viral diarrhea virus (BVDV) and challenged later with bovine herpesvirus type 1 (BHV-1), evaluating the role of MΦs in the development of pathological lesions in this organ. For this purpose, pulmonary lesions were compared between co-infected calves and healthy animals inoculated only with BHV-1 through immunohistochemical (MAC387, TNFα, IL-1α, iNOS, COX-2 and Factor-VIII) and ultrastructural studies. Both groups of calves presented important vascular alterations produced by fibrin microthrombi and platelet aggregations within the blood vessels. These findings were earlier and more severe in the co-infected group, indicating that the concomitance of BVDV and BHV-1 in the lungs disrupts the pulmonary homeostasis by facilitating the establishment of an inflammatory and procoagulant environment modulated by inflammatory mediators released by pulmonary MΦs. In this regard, the co-infected calves, in spite of presenting a greater number of IMΦs than single-infected group, show a significant decrease in iNOS expression coinciding with the presence of more coagulation lesions. Moreover, animals pre-inoculated with BVDV displayed an alteration in the response of pro-inflammatory cytokines (TNFα and IL-1), which play a key role in activating the immune response, as well as in the local cell-mediated response.
authors.affiliation: Department of Comparative Pathology, Veterinary Faculty, University of Córdoba-Agrifood Campus of International Excellence (ceiA3), Edificio Sanidad Animal, Campus de Rabanales, Córdoba 14014, Spain. jcgomez@uco.es.
authors.forename: María A
authors.initials: MA
authors.lastname: Risalde
authors.forename: Verónica
authors.initials: V
authors.lastname: Molina
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Sánchez-Cordón
authors.forename: Fernando
authors.initials: F
authors.lastname: Romero-Palomo
authors.forename: Miriam
authors.initials: M
authors.lastname: Pedrera
authors.forename: Bartolomé
authors.initials: B
authors.lastname: Garfia
authors.forename: José C
authors.initials: JC
authors.lastname: Gómez-Villamandos
mesh_terms: D000818:Animals; D001912:Bovine Virus Diarrhea-Mucosal Disease / Q000473:pathology* / Q000821:virology; D002417:Cattle; D060085:Coinfection / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D001908:Diarrhea Viruses, Bovine Viral / Q000276:immunology*; D004211:Disseminated Intravascular Coagulation / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D006566:Herpesviridae Infections / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D007242:Herpesvirus 1, Bovine / Q000276:immunology*; D008168:Lung / Q000473:pathology* / Q000821:virology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission / Q000662:veterinary; D016133:Polymerase Chain Reaction / Q000662:veterinary