Transcriptional changes in the peripheral blood leukocytes from Brangus cattle before and after tick challenge with Rhipicephalus australis

Abstract

Background Disease emergence and production loss caused by cattle tick infestations have focused attention on genetic selection strategies to breed beef cattle with increased tick resistance. However, the mechanisms behind host responses to tick infestation have not been fully characterised. Hence, this study examined gene expression profiles of peripheral blood leukocytes from tick-naive Brangus steers (Bos taurus x Bos indicus) at 0, 3, and 12 weeks following artificial tick challenge experiments with Rhipicephalus australis larvae. The aim of the study was to investigate the effect of tick infestation on host leukocyte response to explore genes associated with the expression of high and low host resistance to ticks. Results Animals with high (HR, n = 5) and low (LR, n = 5) host resistance were identified after repeated tick challenge. A total of 3644 unique differentially expressed genes (FDR < 0.05) were identified in the comparison of tick-exposed (both HR and LR) and tick-naive steers for the 3-week and 12-week infestation period. Enrichment analyses showed genes were involved in leukocyte chemotaxis, coagulation, and inflammatory response. The IL-17 signalling, and cytokine-cytokine interactions pathways appeared to be relevant in protection and immunopathology to tick challenge. Comparison of HR and LR phenotypes at timepoints of weeks 0, 3, and 12 showed there were 69, 8, and 4 differentially expressed genes, respectively. Most of these genes were related to immune, tissue remodelling, and angiogenesis functions, suggesting this is relevant in the development of resistance or susceptibility to tick challenge. Conclusions This study showed the effect of tick infestation on Brangus cattle with variable phenotypes of host resistance to R. australis ticks. Steers responded to infestation by expressing leukocyte genes related to chemotaxis, cytokine secretion, and inflammatory response. The altered expression of genes from the bovine MHC complex in highly resistant animals at pre- and post- infestation stages also supports the relevance of this genomic region for disease resilience. Overall, this study offers a resource of leukocyte gene expression data on matched tick-naive and tick-infested steers relevant for the improvement of tick resistance in composite cattle.

Application of quantitative proteomics to discover biomarkers for tick resistance in cattle

“…These proteins contributed to complement activation, regulation of activation of membrane attack complex, innate immune response, regulation of phagocytosis and leukocyte-mediated immunity. These findings confirmed the transcriptomics results reported recently ( 25 ), where the differences in leukocyte gene expression between the low and high tick resistance cattle were the highest in naïve cattle. Significantly higher abundance of complement factor proteins in resistant cattle is supported by previous research demonstrating the increased expression of genes encoding multiple complement factors in crossbred resistant cattle ( 38 , 39 ).…”

“…For example, susceptible cattle showed higher abundances of several immunoglobulin-like proteins including C3 isoform following early and prolonged tick infestation. Increased expression of humoral immunity genes has previously been reported in low resistance cattle ( 25 , 39 ), but this type of humoral response has not been associated with protection against ticks, and it was suggested as a part of the immunopathology in susceptible hosts ( 13 ).…”

“…Recently, Mantilla Valdivieso et al. ( 25 ) reported that the leukocyte genes involved in immune responses including complement and coagulation cascades and cell signalling pathways were downregulated in both high and low tick-resistant Brangus cattle over short (3 weeks) and long (12 weeks) infestation periods. The authors suggested that migration of the cell populations expressing these genes out of the peripheral circulation may have caused the pathway downregulation.…”

“…For animal phenotyping based on tick burden, an intensive artificial tick infestation trial was carried out using larvae of a Non-Resistant Field Strain of R. australis , as reported by ( 25 ). Briefly, 30 animals were artificially infested with 10 000 (0.5 g) R. australis larvae applied weekly on the back of each animal for 12 consecutive weeks with a total of 13 infestations, along with concurrent exposure to the natural tick infestation on pastures.…”

“…Recently, Moré et al ( 24 ) identified more than a hundred immune-related genes encoding cytokines, chemokines, CD markers, acute phase proteins, complement proteins, integrins, and transcription factors using a high throughput RNA sequencing technology to compare gene expression in tick-resistant and susceptible Braford cattle. Whereas Mantilla Valdivieso et al ( 25 ) identified genes related to immune, tissue remodelling, and angiogenesis functions from tick-resistant and susceptible Brangus composite breed cattle. In response to tick infestation, transcriptome analyses provide a broader picture of functional activity at the cellular level by summarizing coding and non-coding transcriptional activity and gene expression.…”