Location: Animal Disease ResearchTitle: East coast fever caused by Theileria parva is characterized by macrophage activation associated with vasculitis and respiratory failure
|Frevert, Charles - University Of Washington|
|Nelson, Danielle - Washington State University|
|Morrison, Ivan - University Of Edinburgh|
|Knowles Jr, Donald|
Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/6/2016
Publication Date: 5/19/2016
Citation: Fry, L.M., Schneider, D.A., Frevert, C.W., Nelson, D.D., Morrison, I., Knowles, D.P. 2016. East coast fever caused by Theileria parva is characterized by macrophage activation associated with vasculitis and respiratory failure. PLoS One. doi:10.1371/journal.pone.0156004.
Interpretive Summary: East Coast Fever is caused by the parasite Theileria parva. This parasite is related to the parasites that cause malaria and babesiosis in cattle and humans. Infection of cattle with T. parva is the cause of economic burden to pastoral farmers in Africa and therefore is a threat to global food security. Disease in cattle is characterized by proliferation of lymphocytes infected with T. parva. The data of this manuscript provides critical information concerning other immune cells that participate in disease and in some cases death. Activation of macrophages (a central cell in immunity) occurs in terminal East Coast Fever. This activation and associated inflammation is a new finding and important knowledge in vaccine development. Prior to this work, East Coast Fever was thought to be primary due to proliferation of infected lymphocytes. Components of T. parva chosen for vaccination must not induce macrophage activation.
Technical 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.