Comparative transcriptome profiling of peripheral blood mononuclear cells suggests Protocadherin-1 (PCDH1) as a distinctive innate immunity signature in Sahiwal, Tharparkar and Gir compared to Karan Fries cattle

Abstract

The primary defence mechanism depends on the gene expression profile of the innate immune system. Although Indian cattle breeds appear to have better disease resistance than exotic and crossbred cattle, the molecular evidence is limited. Therefore, the study explored the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) across three indigenous Indian cattle breeds, Sahiwal (SW), Tharparkar (TP), and Gir (GIR), in comparison to a crossbred Karan Fries (KF). RNA sequencing was performed on PBMCs of healthy cattle (n = 3 per breed). Differential gene expression analysis revealed 259 upregulated and 180 downregulated genes in the indigenous breeds than KF. The SW displayed the greatest number of upregulated innate immune genes (n = 23), followed by TP (n = 20) and GIR (n = 5). Among these innate immune genes, Protocadherin-1 (PCDH1), Low-density lipoprotein receptor-related protein 1B (LRP1B), Chemokine C-C motif ligand 8 (CCL8), and Wnt family member 4 (WNT4) were consistently upregulated across all three indigenous breeds. Particularly, the strong upregulation of PCDH1 (>9-fold) along with LRP1B, CCL8, and WNT4 suggests better innate immunity in indigenous breeds than KF. The highest number of downregulated genes was observed in TP (n = 80), followed by SW (n = 71) and GIR (n = 29). Major upregulated pathways included viral protein-cytokine interactions in SW, chemokine and Interleukin-17 (IL-17) signalling pathways in TP, and B cell receptor signalling pathway in GIR. Downregulated pathways included complement cascades in SW and TP, and bacterial invasion of epithelial cells in SW and GIR. Additionally, the genes showing duplications at DNA level (FOSB, NLRP13, and PLAUR) interestingly showed an increased expression in Tharparkar breed and the gene (SLC29A4) having deletions at genome level showed decreased expression in the PBMCs of SW. Overall, this study presents molecular evidence for greater innate immunity of Indian indigenous cattle breeds compared to a crossbred, KF.