TitleChanges in the Molecular and Functional Phenotype of Bovine Monocytes during Infection.
Publication TypeJournal Article
Year of Publication2019
AuthorsBastos, RG, Sears, KP, Dinkel, KD, Knowles, DP, Fry, LM
JournalInfect Immun
Date Published2019 12
KeywordsAnimals, Cattle, Interleukin-10, Interleukin-1beta, Lipopolysaccharides, Monocytes, Parasite Load, Protozoan Vaccines, RNA, Messenger, T-Lymphocytes, Cytotoxic, Theileria parva, Theileriasis, Tumor Necrosis Factor-alpha

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 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 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 infection. 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 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. stimulation with schizont-infected cells or 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 schizont-infected cells. In conclusion, we demonstrate that 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 candidate vaccines.

Alternate JournalInfect Immun
PubMed ID31570561
PubMed Central IDPMC6867863