Biomarkers to predict severity of bovine e.coli mastitis in the periparturient period: bridging the gap between genotype and phenotype

The causes of periparturient (PP) E.coli mastitis in lactating cows are complex and multifactorial (Burvenich et al., 2007). The disease is accompanied by a large variation in clinical symptoms varying from mild/moderate, to severe life-threatening sepsis. There is a small subpopulation of severely affected cows that suffer from unbalanced inflammation. It is now accepted that severity of PP E.coli mastitis is mainly determined by cow factors (Burvenich et al., 2003). Studies on isolated blood neutrophils (PMN) of healthy cows before intramammary infection with alive E.coli bacteria, showed that chemotaxis (Lohuis et al., 1990; Kremer et al., 1993) and the capacity to produce reactive oxygen species (Heyneman et al., 1990) before challenge is negatively correlated with severity and positively with pathogen elimination. At least three major issues can be discerned from these studies: (I) the role of the alteration of pre-infection PMN function in the outcome of PP E.coli mastitis. Since the nineties many studies have contributed to the understanding of the alteration of PP PMN function and viability. In vitro effects of nonesterified fatty acids, beta hydroxybutyrate, estradiol, progesterone, glucocorticoids and IGF were studied (Lamote et al., 2004; Scalia et al., 2006; Sander et al., 2011). (II) The study of potential links with other diseases during the same period. The PP period is a critical period for animal welfare and dairy economics. (III) Identification of one or more biomarkers (BM) to characterize E.coli mastitis specifically and their potential role in the management and health care of cows in general. In contrast to the afore-mentioned issues only a few studies are dealing with predictability of severity of PP diseases. This review will analyze some historical studies for potential BM discovery based on PMN function and relating gene expression to its phenotypic outcome (e.g.: CD11/CD18, alkalin phosphatase by van Werven et al., 1997, CD25-expression by Zoldan et al., 2014, and serum proteomics by Cairoli et al., 2006). It will also focus on genome- and epigenome- based tools and discusses advantages, limitations and future prospects. The potential utility of BM in experimental research and/or field studies will also be highlighted (see Figure 1).