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

John D. Lippolis, Ellie J. Putz, Timothy A. Reinhardt, Eduardo Casas, Wanda J. Weber, Brian A. Crooker

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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 Holsteins (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 Escherichia coli challenge model. Primiparous UH (n = 5) and CH (n = 7) cows received 430 cfu of 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, somatic cell count and BSA concentrations, complete blood cell counts, rectal temperature, and serum and milk whey cytokine (IL-1β 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 a false discovery rate of P < 0.05 and a delta log 2 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 somatic cell count 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 BSA, IL-1β, 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 postinfusion sampling times was consistently greater (4- to 90-fold) in CH than in UH cows. A key difference between the immune reaction of the 2 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.

Original languageEnglish (US)
Pages (from-to)5435-5448
Number of pages14
JournalJournal of Dairy Science
Issue number6
StatePublished - Jun 2022

Bibliographical note

Funding Information:
This work was supported in part by USDA-Agricultural Research Service project 5030-32000-115-000-D, the Minnesota Agricultural Experiment Station, a Grant-in-Aid award (#22965) from the Office of the Vice President for Research, University of Minnesota, and a grant from the Rapid Agricultural Response Fund program of the Minnesota State Legislature and Minnesota Agricultural Experiment Station. Seth Melson was supported by an Undergraduate Research Opportunity Program grant from the University of Minnesota. The authors appreciate the excellent animal care and courteous assistance provided throughout the study by the National Animal Disease Center (NADC; Ames, IA) staff. We especially acknowledge and appreciate the valuable animal sampling and technical assistance provide by Duane Zimmerman and Tera Nyholm (NADC) and laboratory assistance of Seth Melson (University of Minnesota, St. Paul). Assistance with RNA sequence data processing was provided by Hao Ma (NADC). Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendations or endorsement by the USDA. USDA is an equal opportunity provider and employer. The USDA determines the research priorities of all research that it funds. Publication of research is subject to review of USDA officials. Specific study design, data collection, data analysis, and preparation of the manuscript are under the control of the individual researchers. The authors have not stated any conflicts of interest.

Publisher Copyright:
© 2022 American Dairy Science Association


  • Holstein genotype
  • experimental mastitis
  • immune function
  • Escherichia coli
  • Escherichia coli Infections/veterinary
  • Genotype
  • Immunity, Innate/genetics
  • Milk/metabolism
  • Animals
  • Mammary Glands, Animal/metabolism
  • Cattle
  • Interleukin-6/metabolism
  • Cattle Diseases/metabolism
  • Female
  • Mastitis, Bovine/microbiology

PubMed: MeSH publication types

  • Journal Article


Dive into the research topics of 'Effect of Holstein genotype on immune response to an intramammary Escherichia coli challenge'. Together they form a unique fingerprint.

Cite this