Functional Adaptations of the Transcriptome to Mastitis-Causing Pathogens: The Mammary Gland and Beyond

Abstract

Application of microarrays to the study of intramammary infections in recent years has provided a wealth of fundamental information on the transcriptomics adaptation of tissue/cells to the disease. Due to its heavy toll on productivity and health of the animal, in vivo and in vitro transcriptomics works involving different mastitis-causing pathogens have been conducted on the mammary gland, primarily on livestock species such as cow and sheep, with few studies in non-ruminants. However, the response to an infectious challenge originating in the mammary gland elicits systemic responses in the animal and encompasses tissues such as liver and immune cells in the circulation, with also potential effects on other tissues such as adipose. The susceptibility of the animal to develop mastitis likely is affected by factors beyond the mammary gland, e.g. negative energy balance as it occurs around parturition. Objectives of this review are to discuss the use of systems biology concepts for the holistic study of animal responses to intramammary infection; providing an update of recent work using transcriptomics to study mammary and peripheral tissue (i.e. liver) as well as neutrophils and macrophage responses to mastitis-causing pathogens; discuss the effect of negative energy balance on mastitis predisposition; and analyze the bovine and murine mammary innate-immune responses during lactation and involution using a novel functional analysis approach to uncover potential predisposing factors to mastitis throughout an animal's productive life.

Generation of an index for physiological imbalance and its use as a predictor of primary disease in dairy cows during early lactation

“…The SDiff was higher for PI and plasma NEFA for most diseases, especially all diseases (Table 4), and suggests that changes in PI and plasma NEFA are better predictors of disease risk than EBAL, plasma BHBA, and glucose after parturition. Our results show that an index for PI, based on plasma NEFA, BHBA, and glucose, relates to risk for most diseases and supports the growing evidence linking overall metabolic status to risk of infectious Loor et al, 2011;Ingvartsen and Moyes, 2012) and noninfectious diseases (Ingvartsen, 2006;Huzzey et al, 2011) in dairy cows. The study showed that prepartal degree of PI was linked to disease after calving.…”

“…For decades, researchers have used calculated energy balance (EBAL), primarily based on DMI, milk yield, and milk components, as the gold standard to reflect the degree of change in energy mobilization during early lactation in relation to risk of disease. Studies have shown that calculated negative EBAL, and the metabolites that characterize negative EBAL, are associated with reduced fertility (Walsh et al, 2011), immune function and increased risk of some infectious Loor et al, 2011) and noninfectious diseases (Ingvartsen, 2006;Huzzey et al, 2011). We hypothesize that an index for PI, based on several metabolites in blood, will more directly relate to mechanisms associated with the development of several diseases during early lactation and, in turn, will be a better predictor of risk of disease than, for example, standard methods used to calculate EBAL described previously (National Research Council, 2001;Friggens et al, 2007) or the use of individual metabolites alone.…”

Integrative Analyses of Hepatic Differentially Expressed Genes and Blood Biomarkers during the Peripartal Period between Dairy Cows Overfed or Restricted-Fed Energy Prepartum

“…This innate immune response pathway has been previously reported to be among the most-activated in several studies involving mammary gland bacterial infection [50]. Innate immune response-related pathways including ‘Toll-like receptor’ (File S2), but especially the pathways related to the immune cell migration or activity (e.g., ‘Leukocyte transendothelial migration’, and ‘T cell receptor signaling pathway’), were more induced in OF vs. RE, particularly at +14 d. The DIA analysis of GO BP indicated a larger activation of macrophage in OF vs. RE but, contrary to the KEGG pathway results, indicated a more induced chemotaxis of some of the immune cells in RE vs. OF at +14 d (File S4).…”

Milk Protein Synthesis in the Lactating Mammary Gland: Insights from Transcriptomics Analyses

“…Dairy cows have a moderate, although consistent, increase only for the genes coding for lactoperoxidase and lactoferrin ( Figure 2). Collectively, those data might indicate an overall increase in the innate immune response of the mammary gland during lactation [103] and/or an increase in milk antimicrobial activity in all species during lactation. It appears that the goat, mouse and pig have a higher antimicrobial activity in the milk due to the spike of specific activities (i.e., lactoperoxidase in goat and lactoferrin in monogastric).…”