Immune defenses of the mammary gland epithelium of dairy ruminants

Abstract

The epithelium of the mammary gland (MG) fulfills three major functions: nutrition of progeny, transfer of immunity from mother to newborn, and its own defense against infection. The defense function of the epithelium requires the cooperation of mammary epithelial cells (MECs) with intraepithelial leucocytes, macrophages, DCs, and resident lymphocytes. The MG is characterized by the secretion of a large amount of a nutrient liquid in which certain bacteria can proliferate and reach a considerable bacterial load, which has conditioned how the udder reacts against bacterial invasions. This review presents how the mammary epithelium perceives bacteria, and how it responds to the main bacterial genera associated with mastitis. MECs are able to detect the presence of actively multiplying bacteria in the lumen of the gland: they express pattern recognition receptors (PRRs) that recognize microbe-associated molecular patterns (MAMPs) released by the growing bacteria. Interactions with intraepithelial leucocytes fine-tune MECs responses. Following the onset of inflammation, new interactions are established with lymphocytes and neutrophils recruited from the blood. The mammary epithelium also identifies and responds to antigens, which supposes an antigen-presenting capacity. Its responses can be manipulated with drugs, plant extracts, probiotics, and immune modifiers, in order to increase its defense capacities or reduce the damage related to inflammation. Numerous studies have established that the mammary epithelium is a genuine effector of both innate and adaptive immunity. However, knowledge gaps remain and newly available tools offer the prospect of exciting research to unravel and exploit the multiple capacities of this particular epithelium.

Immune profiling of experimental murine mastitis reveals conserved response to mammary pathogenic Escherichia coli, Mycoplasma bovis, and Streptococcus uberis

“…The role pericytes and telocytes play in neutrophil recruitment to the mammary gland is currently unknown; however, transgenic mice presented in our study can expedite this avenue of research. MAMPs released by colonizing bacteria activate MAE cells and alveolar macrophages, causing them to release inflammatory mediators, chemo attractants, and chemokines which are the enablers of neutrophil trafficking (Rainard et al, 2022). Our gene expression results are well corroborated with previous in vitro and in vivo studies showing that activation of mammary inflammation by MAMPs is mediated by TNFɑ, IL-1β, and the NFkB and IL6-JAK-STAT3 pathways (Kobayashi et al, 2013;Sharifi et al, 2018;Weller et al, 2019;Passe Pereira et al, 2021).…”

“…These acute pathological changes recapitulate the disease processes observed in field cases and underscore the translational utility of the murine model systems. Moreover, the transcriptional response observed in our model systems is highly similar to those reported in numerous studies in dairy animals (Younis et al, 2016;Rainard et al, 2022). It is generally accepted that mastitis is a MAMP-mediated disease and that specialized bacterial virulence factors other than fitness factors that enable initial growth and colonization are unlikely to play a role in acute mastitis (Keane, 2019;Salamon et al, 2020).…”

“…Invading bacteria require to grow in milk and withstand innate antimicrobial mechanisms active in the milk such as the complement system and essential nutrients chelators. Next, inflammation is activated by microbial-associated molecular patterns (MAMPs) released by the growing bacteria leading to massive recruitment of blood neutrophils into the alveolar and milk spaces (Rainard et al, 2022). MAMPs activate a plethora of innate receptors and signaling systems in mammary epithelial cells (MEC) and alveolar macrophages which are the first line of response to the invading pathogens.…”

Lipoproteins Are Potent Activators of Nuclear Factor Kappa B in Mammary Epithelial Cells and Virulence Factors in Mycoplasma bovis Mastitis

“…In the present study, M. bovis 161791 field strain was successfully used to establish and characterize in vitro murine MEC-based and in vivo murine mastitis model systems (Figures 1 and 2). MECs play a major role in the innate immune system of mammary gland providing the first line of defense against invading pathogens and their MAMPs [61]. Interaction between MAMPs and PRRs, expressed on the host cells, leads to the activation of several signaling components, including NF-κB, which is a major regulator of inflammation in the mammary gland regulating more than 200 dependent genes, such as cytokines, chemokines, and other inflammatory mediators and modulators [36,62].…”

Genetic polymorphisms in immune- and inflammation-associated genes and their association with bovine mastitis resistance/susceptibility

“…Normally, the mammary gland performs three functions, including the provision of nutrition to offspring in the form of milk, the transfer of immunity from mother to offspring through immunoglobulins in milk, and the provision of protection against microbes (1,2). Bovine mastitis, the inflammation of mammary glands, occurs when the udder is exposed to any physical injury or pathogenic microorganisms (3).…”