- Oral presentation
- Open Access
Immunogenomics Approaches to Understanding Periparturient Mastitis Susceptibility in Dairy Cows
© The Author(s); licensee BioMed Central Ltd. 2003
Published: 31 March 2003
Studies comparing in vitro functional capacities of leukocytes from non-parturient and periparturient dairy cows have provided substantial evidence that systemic and local mammary immune defenses are deficient around parturition. This evidence has lead to the reasonable hypothesis that immune deficiency underlies the heightened mastitis susceptibility of periparturient cows. Nutrition and vaccine studies partially substantiate this hypothesis, showing that dietary antioxidant supplementation and rigorous immunization regimes can bolster innate and humoral immunity to the point that mastitis severity and time for return to normal milk production are reduced. However, completely effective resolution of this significant production disease has not been achieved because so little is understood about its complex etiology. In particular, we possess almost no knowledge of how or why immune cells responding to parturient physiology end up with deficient functional capacities. Therefore, a thorough understanding of leukocyte biology in periparturient dairy cows would seem a critical goal for future development of effective mastitis prevention strategies. Recently, our group has used a combination of functional genomics techniques to interrogate leukocyte RNA for global gene expression changes occurring around parturition. Leukocyte RNA was obtained for this work at multiple times before, during, and after parturition. Preliminary screening for differentially expressed genes using DDRT-PCR, dot blot, and slot blot analyses revealed profound reductions in neutrophil expression of 13 transcripts putatively identified by cDNA sequence and BLAST analyses as genes required for cellular adhesion, energy metabolism, and gene transcription. This is problematic because mammary defense against mastitis-causing bacteria depends on adequate activation, migration, and phagocytic and killing capacities of blood-derived neutrophils. Further interrogation of the leukocyte RNA using cDNA microarrays spotted with >700 unique genes from our group's bovine total leukocyte cDNA library revealed ~30 additional genes with 3-fold or higher expression changes at parturition. Top BLAST results identified these genes as members of nuclear transcription factors, growth and differentiation factors, enzymes and cofactors of energy metabolism, antigen presentation molecules, cytokine receptors, adhesion molecules, coagulation factors, and protein kinases. Preliminary analyses also showed that many of the down-regulated neutrophil genes correlated strongly with massive fluctuations in blood concentrations of cortisol, progesterone, and estrogen. These potent steroid hormones have well-established gene regulatory actions in other cell systems, so it was not surprising that they also associated with altered gene expression in neutrophils. Chronic shifts in key nutrient partitioning hormones and nutrients in periparturient cows may also affect the expression of critical leukocyte genes, perhaps even up to the time of peak lactation. We plan to test these hypotheses in future studies. Once the most critical candidate genes of periparturient immune deficiency have been identified, these can be tested for polymorphism and as potential regulatory targets to improve mastitis resistance through novel genetic selection, nutritional, pharmacological strategies.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.