Publikationsdatenbank

Upregulation of haematopoetic cell kinase (Hck) activity by a secreted parasite effector protein (Ta9) drives proliferation of Theileria annulata-transformed leukocytes (2025)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Tajeri, Shahin (WE 13)

Shiels, Brian

Langsley, Gordon

Nijhof, Ard Menzo (WE 13)

Quelle

Microbial pathogenesis

Bandzählung: 199

Seiten: 107252

ISSN: 1096-1208

Sprache

Englisch

Verweise

URL (Volltext): https://www.sciencedirect.com/science/article/pii/S0882401024007198?via%3Dihub

DOI: 10.1016/j.micpath.2024.107252

Pubmed: 39730099

Kontakt

Institut für Parasitologie und Tropenveterinärmedizin

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 62310
parasitologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Reversible transformation of bovine leukocytes by the intracellular parasites Theileria annulata and Theileria parva is central to pathogenesis of the diseases they cause, tropical theileriosis and East Coast Fever, respectively. Parasite-dependent constitutive activation of major host transcription factors such as AP-1 (Activating Protein 1) and NF-κB (Nuclear Factor-Kappa B) sustains the transformed state. Although parasite interaction with host cell signaling pathways upstream of AP-1 have been studied, the precise contribution of Theileria encoded factors capable of modulating AP-1 transcriptional activity, and other infection-altered signaling pathways is not fully understood. We previously showed that the Ta9 protein from T. annulata (TA15705) is secreted into the host cell cytoplasm and contributes to infection-induced AP-1 transcriptional activity. The current study employed RNA-seq to investigate the ability of ectopically expressed Ta9 to modulate the gene transcription profile of a bovine macrophage cell line, BoMac. RNA-seq identified 560 (400 upregulated and 160 downregulated) differentially expressed genes. KEGG analysis predicted a high number of upregulated genes associated with carcinogenesis such as CCND1, CDKN1A, ETV4, ETV5, FLI1, FRA1, GLI2, GRO1, HCK, IL7R, MYBL1, MYCN, PIM1 and TAL1. Ta9 introduction also affected genes associated with proinflammatory processes such as cytokines, chemokines, growth factors and metalloproteinases. Enrichment analysis of differentially expressed genes revealed that Ta9 is potentially involved in activating other host cell signaling pathways in addition to those that lead to induction of AP-1. Comparing our data with data on differentially expressed BoMac genes modulated by the secreted TashAT2 factor of T. annulata identified the gene encoding the tyrosine protein kinase hematopoietic cell kinase (HCK) as common to both data sets. HCK is essential for the proliferation of T. parva-transformed B cells and herein, we demonstrate that enzymatic activity of HCK is also essential for T. annulata- and T. lestoquardi-transformed macrophage proliferation.