It is well established that a primary component of East Coast Fever is parasite-driven proliferation of the cow’s lymphocytes.  Unknown until now was the important role of the cow’s macrophages in driving an inflammatory response resulting in injury to blood vessels in the lung and respiratory failure.

The “cancer-like” nature of East Coast Fever is due to the ability of Theileria parva, the causal parasite, to cause the cow’s lymphocytes to proliferate.

Although lymphocyte proliferation has long been credited as the cause of death in East Coast Fever, a new article from ECF consortium researchers shows that macrophage-driven inflammation, likely in response to the parasite, is the cause  of tissue damage and death in East Coast Fever.

This intense macrophage reaction is part of a process referred to as “macrophage activation syndrome,” and is responsible for an “inflammatory storm” that leads to damaged blood vessels in the lung and respiratory failure.

Blog post contributed by Dnn Knowles, Washington State University

Download the open access article

Fry, L.M., Schneider, D.A., Frevert, C.W., Nelson, D.D., Morrison, W.I. and Knowles, D.P. 2016. East Coast fever caused by Theileria parva is characterized by macrophage activation associated with vasculitis and respiratory failure. PLoS One 11(5):e0156004. http://dx.doi.org/10.1371/journal.pone.0156004

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.