Effect of Holstein genotype on immune response to an intramammary Escherichia coli challenge

Authors: Lippolis, John; PUTZ, ELLIE - Oak Ridge Institute For Science And Education (ORISE); Reinhardt, Timothy; Casas, Eduardo; WEBER, WANDA - University Of Minnesota; CROOKER, BRIAN - University Of Minnesota

Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/8/2022
Publication Date: 5/1/2022
Citation: Lippolis, J.D., Putz, E.J., Reinhardt, T.A., Casas, E., Weber, W.J., Crooker, B.A. 2022. Effect of Holstein genotype on immune response to an intramammary Escherichia coli challenge. Journal of Dairy Science. 105(6):5435-5448. https://doi.org/10.3168/jds.2021-21166.
DOI: https://doi.org/10.3168/jds.2021-21166

Interpretive Summary: Cows with genetics equal to that found in 1964 where compared with modern dairy cows for their ability to fight mastitis. We found that dairy cows with 1964 genetic had a significantly reduced disease severity compared to modern cows. Understanding the immune system mechanisms that are present in cows with the genetics of 1964 may help us reintroduce those mechanisms into the modern dairy cow and increase disease resistance.

Technical Abstract: Selective breeding of US dairy cows since the mid-1960s has contributed to remarkable gains in milk yield per cow. This increased milk yield has been associated with an increase in health issues. Since 1964, the University of Minnesota has selectively bred a Holstein herd to maintain genetically static, unselected Holsteins (UH). Comparison of these UH cows with contemporary Holstein (CH) has demonstrated that the UH cows not only produce less milk but also have fewer health concerns than their CH herdmates. The objective of this study was to determine the effects of Holstein genotype on innate immune response in an experimental intramammary E. coli challenge model. Primiparous UH (n= 5) and CH (n = 7) cows received 430 cfu E. coli strain P4 in 1 quarter. Blood and affected quarter milk samples were collected at 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 7, 9 and 11 d relative to E. coli infusion. Rectal temperatures were recorded at each milking through d 4 of the experiment. Milk bacterial counts, SCC and BSA concentrations, complete blood cell counts, rectal temperature, and serum and milk whey cytokine (IL-1ß and IL-6) concentrations were used as metrics to determine infection severity. Longitudinal (repeated) data were analyzed using general linear models with PROC MIXED with day of study as the repeated effect. Whole blood transcriptomes were generated by RNA sequencing. Transcripts with an FDR of P < 0.05 and a delta log2 expression value greater than 0.7 or less than -0.7 were used for functional enrichment analysis. Bacterial counts were consistently greater in milk from CH than UH cows from d 0.25 through d 2.5. Milk SCC increased within 6 h (d 0.25) after E. coli administration in CH and UH cows but did not differ between genotypes after d 1. Rectal body temperature peaked at d 1 in CH and UH cows but was greater in CH cows. Milk bovine serum albumin, IL-1ß and IL-6 concentrations were greater in CH than UH cows after E. coli administration. Blood lymphocyte and neutrophil counts were decreased at 0.5 and 1 d in CH but not in UH cows. The number of differentially expressed transcripts at each of the post-infusion sampling times were consistently greater (4 to 90-fold) in CH than in UH cows. A key difference between the immune reaction of the two genotypes was that the immune response to E. coli was largely contained within the mammary gland of the UH cows but became more systemic in the CH cows. These data demonstrate that UH cows exerted more effective control of E. coli infused into the mammary gland and thus support the hypothesis that selection practices since the mid-1960s have resulted in CH cows with an immune system that is less effective in fighting intramammary infections. Identification of genetic factors associated with enhanced immune functions that differ between the UH and CH cows could contribute to efforts to reintroduce or enhance beneficial components that have been lost or reduced in the CH cows since the mid-1960s.