Genetic variation in CXCR1 haplotypes linked to severity of Streptococcus uberis infection in an experimental challenge model

Mastitis, an inflammation of the mammary gland, costs the dairy industry billions of dollars in lost revenues annually. The prevalence and costs associated with mastitis has made genetic selection methods a target for research. Previous research has identified amino acid changes at positions 122, 207, 245, 327, and 332 in the IL8 receptor, CXCR1, that result in three dominant amino acid haplotypes: VWHKH, VWHRR, and AWQRR. We hypothesize different haplotype combinations influence a cow's resistance, strength, and duration of response to mastitis. To test this, Holstein dairy cows (n = 40) were intramammarily challenged with Streptococcus uberis within 3 d post-calving. All cows developed mastitis based on isolation of S. uberis from the challenged quarter at least twice. All cows with the VWHRR x VWHRR (n = 5) and AWQRR x VWHRR (n = 6) haplotype combinations required antibiotic therapy due to clinical signs of mastitis and tended (P = 0.08) to be different from cows with a VWHRR x VWHKH (n = 6) haplotype combination where only 33.3% required antibiotic therapy. Cows with a VWHRR homozygous haplotype combination displayed significantly higher responses to challenge indicated by elevated S. uberis counts (4340 ± 5,521.9 CFU/mL; P = 0.01), mammary scores (1.1 ± 0.18; P = 0.03), milk scores (0.9 ± 0.17; P = 0.002), and SCC (1,010,832 ± 489,993 cells/mL; P = 0.03). Contrastingly, AWQRR x VWHRR cows had significantly lower S. uberis counts (15.3 ± 16.46 CFU/mL; P = 0.01), mammary scores (0.3 ± 0.16; P = 0.03), milk scores (0 ± 0.15; P = 0.002), and SCC (239,261 ± 92,264.3 cells/mL; P = 0.03). Cows of the VWHKH x VWHRR haplotype combination displayed responses to challenge statistically comparable to other haplotype combinations, but appeared to have an earlier peak in SCC in comparison to all other haplotype combinations. Haplotype combination did not influence milk yield (P = 0.6). Our results suggest using combinations of the SNPs within the CXCR1 gene gives a better indication of a cow's ability to combat S. uberis mastitis and could resolve prior studies' conflicting results focusing on individual SNP.