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ARS Home » Northeast Area » Beltsville, Maryland (BARC) » Beltsville Agricultural Research Center » Animal Genomics and Improvement Laboratory » Research » Publications at this Location » Publication #330193
Title: Neonatal lipopolysaccharide challenge does not diminish the innate immune response to a subsequent lipopolysaccharide challenge in holstein bull calves

Author
item BENJAMIN, A - University Of Vermont
item KORKMAZ, F - University Of Vermont
item Elsasser, Theodore
item KERR, D - University Of Vermont

Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/14/2016
Publication Date: 4/20/2016
Citation: Benjamin, A.L., Korkmaz, F.T., Elsasser, T.H., Kerr, D.E. 2016. Neonatal lipopolysaccharide challenge does not diminish the innate immune response to a subsequent lipopolysaccharide challenge in holstein bull calves. Journal of Dairy Science. 99(7):5750-5763.

Interpretive Summary: Dairy producers are constantly monitoring their cows for any sign of infection in the mammary gland and also vigilant in taking measures to prevent disease in the mammary gland. However over time it has become apparent that different populations of cows respond differently when exposed to potential infecting bacteria and this variability in the infection response complicates the precision with which veterinary treatment can be applied. Just like in humans, the response to an infecting organism by a dairy cow is greatly influenced by the nature of how the genes of that animal are turned on or off as a function of the infection process. The physical presentation of those gene responses in an animal defines what is called the phenotype of that animal for the particular trait being observed during the response to infection. An additional level on complication is added to the capability of accurately assessing the phenotype of infection responses because we also know now that many challenges that animals experience early in life can have a lasting effect to modify future responses of the animal to similar challenges. The present research looked at how an early life exposure to a lipopolysaccharide, disease-related molecule that comes from some types of bacteria, can influence an exposure to the same agent early in life. Researchers at USDA-ARS Beltsville, Maryland and the University of Vermont used two populations of calves that were determined to have at birth either a potential to have a high response to infection or a low response to an infection challenge. The researchers observed that calves low responding calves characteristically had lower responses to the first experimental challenge with the lipopolysaccharide that the high responding population but upon rechallenge with the same lipopolysaccharide 25 days later, the responses of both populations were equal. These data support the idea that how animals respond to infection stress later in life can be affected by what they experience early in life. Such observations, while needing more investigation, suggest that management of health in food animals should consider what early life experiences and challenges the animals were exposed to.

Technical Abstract: The innate immune response following experimental mastitis is quite variable between individual dairy cattle. An inflammatory response that minimizes collateral damage to the mammary gland while still effectively resolving the infection following pathogen exposure is beneficial to dairy producers. The ability of a lipopolysaccharide (LPS) exposure in early life to generate a low-responding phenotype and thus reduce the inflammatory response to a later-life LPS challenge was investigated in neonatal bull calves. Ten Holstein bull calves were randomly assigned to either an early life LPS (ELL) group (n = 5) or an early life saline (ELS) group (n = 5). At 7 d of age, calves received either LPS or saline, and at 32 d of age, all calves were challenged with an intravenous dose of LPS to determine the effect of the early life treatment (LPS or saline) on the immune response generated toward a subsequent LPS challenge. Dermal fibroblast and monocyte-derived macrophage cultures from each calf were established at age 20 and 27 d, respectively, to model sustained effects from the early life LPS exposure on gene expression and protein production of components within the LPS response pathway. The ELL calves had greater levels of plasma IL-6 and tumor necrosis factor-a than the ELS calves following the early life LPS or saline treatments. However, levels of these 2 immune markers were similar between ELL and ELS calves when both groups were subsequently challenged with LPS. A comparison of the in vitro LPS responses of the ELL and ELS calves revealed similar patterns of protein production and gene expression following an LPS challenge of both dermal fibroblast and monocyte-derived macrophage cultures established from the treatment groups. Whereas an early life exposure to LPS did not result in a dampened inflammatory response toward a later LPS challenge in these neonatal bull calves, the potential that exposure to inflammation or stress in early life or in utero can create an offspring with a low-responding phenotype as an adult is intriguing and has been documented in rodents. Further work is needed to determine if an inflammatory exposure in utero in a dairy animal would result in a low-responding innate immune phenotype.