title: East Coast Fever Caused by Theileria parva Is Characterized by Macrophage Activation Associated with Vasculitis and Respiratory Failure.
abstract: Respiratory failure and death in East Coast Fever (ECF), a clinical syndrome of African cattle caused by the apicomplexan parasite Theileria parva, has historically been attributed to pulmonary infiltration by infected lymphocytes. However, immunohistochemical staining of tissue from T. parva infected cattle revealed large numbers of CD3- and CD20-negative intralesional mononuclear cells. Due to this finding, we hypothesized that macrophages play an important role in Theileria parva disease pathogenesis. Data presented here demonstrates that terminal ECF in both Holstein and Boran cattle is largely due to multisystemic histiocytic responses and resultant tissue damage. Furthermore, the combination of these histologic changes with the clinical findings, including lymphadenopathy, prolonged pyrexia, multi-lineage leukopenia, and thrombocytopenia is consistent with macrophage activation syndrome. All animals that succumbed to infection exhibited lymphohistiocytic vasculitis of small to medium caliber blood and lymphatic vessels. In pulmonary, lymphoid, splenic and hepatic tissues from Holstein cattle, the majority of intralesional macrophages were positive for CD163, and often expressed large amounts of IL-17. These data define a terminal ECF pathogenesis in which parasite-driven lymphoproliferation leads to secondary systemic macrophage activation syndrome, mononuclear vasculitis, pulmonary edema, respiratory failure and death. The accompanying macrophage phenotype defined by CD163 and IL-17 is presented in the context of this pathogenesis.
authors.affiliation: Animal Disease Research Unit, Agricultural Research Service, US Department of Agriculture, Pullman, Washington, United States of America.|Department of Veterinary Microbiology & Pathology, Washington State University, Pullman, Washington, United States of America.
authors.forename: Lindsay M
authors.identifier: 0000-0003-0938-9254
authors.initials: LM
authors.lastname: Fry
authors.affiliation: Animal Disease Research Unit, Agricultural Research Service, US Department of Agriculture, Pullman, Washington, United States of America.|Department of Veterinary Microbiology & Pathology, Washington State University, Pullman, Washington, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Schneider
authors.affiliation: Department of Comparative Medicine Center of Lung Biology, University of Washington School of Medicine, Seattle, Washington, United States of America.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Frevert
authors.affiliation: Department of Veterinary Microbiology & Pathology, Washington State University, Pullman, Washington, United States of America.
authors.forename: Danielle D
authors.initials: DD
authors.lastname: Nelson
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, United Kingdom.
authors.forename: W Ivan
authors.initials: WI
authors.lastname: Morrison
authors.affiliation: Animal Disease Research Unit, Agricultural Research Service, US Department of Agriculture, Pullman, Washington, United States of America.|Department of Veterinary Microbiology & Pathology, Washington State University, Pullman, Washington, United States of America.
authors.forename: Donald P
authors.initials: DP
authors.lastname: Knowles
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D001808:Blood Vessels / Q000473:pathology; D002417:Cattle; D005334:Fever / Q000209:etiology / Q000662:veterinary*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D042601:Lymphatic Vessels / Q000473:pathology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D013801:Theileriasis / Q000150:complications / Q000276:immunology / Q000473:pathology*; D014657:Vasculitis / Q000209:etiology / Q000662:veterinary; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D020381:Interleukin-17; D011956:Receptors, Cell Surface