Allelic Variation in Protein Tyrosine Phosphatase Receptor Type-C in Cattle Influences Erythrocyte, Leukocyte and Humoral Responses to Infestation With the Cattle Tick Rhipicephalus australis.

Nicholas N Jonsson,Louise A Jackson,Constantin Constantinoiu,Emily F Mantilla Valdivieso,David K Cox,Emily K Piper,Elizabeth M Ross,Michael J Stear,Ala E Tabor

doi:10.3389/fimmu.2021.675979

Abstract

The protein tyrosine phosphatase receptor type-C (PTPRC) gene encodes the common leukocyte antigen (CD45) receptor. CD45 affects cell adhesion, migration, cytokine signalling, cell development, and activation state. Four families of the gene have been identified in cattle: a taurine group (Family 1), two indicine groups (Families 2 and 4) and an African “taurindicine” group (Family 3). Host resistance in cattle to infestation with ticks is moderately heritable and primarily manifests as prevention of attachment and feeding by larvae. This study was conducted to describe the effects of PTPRC genotype on immune-response phenotypes in cattle that display a variable immune responsiveness to ticks. Thirty tick-naïve Santa-Gertrudis cattle (a stabilized composite of 5/8 taurine and 3/8 indicine) were artificially infested with ticks weekly for 13 weeks and ranked according to their tick counts. Blood samples were taken from control and tick-challenged cattle immediately before, then at 21 d after infestation and each subsequent week for 9 weeks. Assays included erythrocyte profiles, white blood cell counts, the percentage of cellular subsets comprising the peripheral blood mononuclear cell (PBMC) population, and the ability of PBMC to recognize and proliferate in response to stimulation with tick antigens in vitro. The cattle were PTPRC genotyped using a RFLP assay that differentiated Family 1 and 3 together (220 bp), from Family 2 (462 bp), and from Family 4 (486 bp). The PTPRC allele frequencies were Family 1/3 = 0.34; Family 2 = 0.47; Family 4 = 0.19. There was no significant association between PTPRC genotype and tick count. Each copy of the Family 1/3 allele significantly decreased total leucocyte count (WCC) and CD8+ cells. Increasing dosage of Family 2 alleles significantly increased red blood cell count (RCC), haematocrit (PCV), and haemoglobin (Hb) concentration in blood. Increasing dosage of the Family 4 allele was associated with increased WCC, reduced RCC, reduced PCV and reduced Hb. Homozygote Family 1/3 animals had consistently lower IgG1 in response to tick Ag than homozygote Family 2 animals. The PTPRC genotype influences the bovine immune response to ticks but was not associated with the observed variation in resistance to tick infestation in this study.

Highlights

PTPRC or protein tyrosine phosphatase receptor-type C, known as CD45, or leukocyte common antigen (LCA) is a key component of the signal transduction cascade in immune cells [1]
They found that allelic polymorphisms in CD45 constituted the basis for differential antibody staining in peripheral blood leukocytes from cattle of African, European, and Indian origin, and suggested that polymorphism might be associated with tolerance to regionally endemic pathogens
We genotyped PTPRC (CD45) for all the original animals in the trial and found that there was no significant relationship between tick count and the dosage of any one of the three differentiable alleles, large differences in erythrocyte, leukocyte and humoral responses were observed among PTPRC genotypes: the indicine Family 2 [462] allele was associated with a more robust erythron; the “taurindicine” Family 1 allele [220] was associated with lower leukocyte count, lower % gated CD8+ cells, and lower IgG1 recognition of tick-specific Ag

Summary

Introduction

PTPRC or protein tyrosine phosphatase receptor-type C, known as CD45, or leukocyte common antigen (LCA) is a key component of the signal transduction cascade in immune cells [1]. The smallest isoform is CD45RO of approximately 180 kDa, lacking all of the alternatively spliced exons, whereas the largest isoform that includes all three exons – CD45RABC is about 240 kDa and heavily glycosylated [1, 3, 5] In addition to these variably spliced domains, the protein comprises three fibronectin type III (FN3) repeats, a short transmembrane domain, and a cytoplasmic region of two tandemly duplicated PTPase homology domains (D1 and D2), in which only D1 is catalytically active [3]. Ballingall et al [2] initially considered PTPRC as one of several genes that might influence the diverse responses of African and Asian cattle to endemic pathogens in Africa They noted that peripheral blood leukocytes from African and European taurine cattle had similar CD45RO antibody staining patterns whereas in indicine cattle, the pattern was variable. The pattern of staining corresponded with four distinct allelic families of PTPRC: B. taurus, Bos indicus (×2), and cattle of African origin [2, 7]

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