Abstract
Theileria parva is the causative agent of East Coast fever (ECF), a tick-borne disease that kills over a million cattle each year in sub-Saharan Africa. Immune protection against T. parva involves a CD8+ cytotoxic T cell response to parasite-infected cells. However, there is currently a paucity of knowledge regarding the role played by innate immune cells in ECF pathogenesis and T. parva control. Here, we demonstrate an increase in intermediate monocytes (CD14++ CD16+) with a concomitant decrease in the classical (CD14++ CD16-) and nonclassical (CD14+ CD16+) subsets at 12 days postinfection (dpi) during lethal infection but not during nonlethal T. parva infection. Ex vivo analyses of monocytes demonstrated upregulation of interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) mRNA and increased nitric oxide production during T. parva lethal infection compared to nonlethal infection at 10 dpi. Interestingly, no significant differences in peripheral blood parasite loads were observed between lethally and nonlethally infected animals at 12 dpi. In vitro stimulation with T. parva schizont-infected cells or Escherichia coli lipopolysaccharide (LPS) resulted in significant upregulation of IL-1β production by monocytes from lethally infected cattle compared to those from nonlethally infected animals. Strikingly, monocytes from lethally infected animals produced significant amounts of IL-10 mRNA after stimulation with T. parva schizont-infected cells. In conclusion, we demonstrate that T. parva infection leads to alterations in the molecular and functional phenotypes of bovine monocytes. Importantly, since these changes primarily occur in lethal infection, they can serve as biomarkers for ECF progression and severity, thereby aiding in the standardization of protection assessment for T. parva candidate vaccines.
Highlights
Theileria parva is the causative agent of East Coast fever (ECF), a tickborne disease that kills over a million cattle each year in sub-Saharan Africa
In this study, we sought to investigate changes in the molecular and functional phenotypes of bovine monocytes during T. parva infection
By comparing monocytes from cattle undergoing lethal T. parva infection and nonlethal infection, our data demonstrate significant alterations in monocyte phenotype and function during acute infection
Summary
Theileria parva is the causative agent of East Coast fever (ECF), a tickborne disease that kills over a million cattle each year in sub-Saharan Africa. There is currently a paucity of knowledge regarding the role played by innate immune cells in ECF pathogenesis and T. parva control. We demonstrate an increase in intermediate monocytes (CD14ϩϩ CD16ϩ) with a concomitant decrease in the classical (CD14ϩϩ CD16Ϫ) and nonclassical (CD14ϩ CD16ϩ) subsets at 12 days postinfection (dpi) during lethal infection but not during nonlethal T. parva infection. In vitro stimulation with T. parva schizont-infected cells or Escherichia coli lipopolysaccharide (LPS) resulted in significant upregulation of IL-1 production by monocytes from lethally infected cattle compared to those from nonlethally infected animals. We demonstrate that T. parva infection leads to alterations in the molecular and functional phenotypes of bovine monocytes Since these changes primarily occur in lethal infection, they can serve as biomarkers for ECF progression and severity, thereby aiding in the standardization of protection assessment for T. parva candidate vaccines. As an intracellular hemoprotozoan parasite, T. parva provides an interesting model to investigate innate immune mechanisms, including monocyte function, for related hemoparasitic infections, including Babesia spp. and Plasmodium spp
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