The Mammary Microenvironment in Mastitis in Humans, Dairy Ruminants, Rabbits and Rodents: A One Health Focus

Abstract

The One Health concept promotes integrated evaluation of human, animal, and environmental health questions to expedite advances benefiting all species. A recognition of the multi-species impact of mastitis as a painful condition with welfare implications leads us to suggest that mastitis is an ideal target for a One Health approach. In this review, we will evaluate the role of the mammary microenvironment in mastitis in humans, ruminants and rabbits, where appropriate also drawing on studies utilising laboratory animal models. We will examine subclinical mastitis, clinical lactational mastitis, and involution-associated, or dry period, mastitis, highlighting important anatomical and immunological species differences. We will synthesise knowledge gained across different species, comparing and contrasting disease presentation. Subclinical mastitis (SCM) is characterised by elevated Na/K ratio, and increased milk IL-8 concentrations. SCM affecting the breastfeeding mother may result in modulation of infant mucosal immune system development, whilst in ruminants notable milk production losses may ensue. In the case of clinical lactational mastitis, we will focus on mastitis caused by Staphylococcus aureus and Escherichia coli. Understanding of the pathogenesis of involution-associated mastitis requires characterization of the structural and molecular changes occurring during involution and we will review these changes across species. We speculate that milk accumulation may act as a nidus for infection, and that the involution 'wound healing phenotype' may render the tissue susceptible to bacterial infection. We will discuss the impact of concurrent pregnancy and a 'parallel pregnancy and involution signature' during bovine mammary involution.

Keywords: Mammary gland; Mastitis; Microenvironment; One Health; Rabbit; Ruminant; Sheep.

Fig. 1

The mammary microenvironment in mastitis in a third lactation Holstein Friesian cow, 46 dL. (a) Multifocal mammary alveoli are engorged with numerous predominantly degenerate neutrophils (*). Haematoxylin and eosin stain; scale bar: 300 μm. (b) Severely affected alveoli with myriad neutrophils (*) exhibit partial loss of the luminal epithelial lining (arrows) although the partial remnants of the mammary epithelial lining remain (double headed arrow). Haematoxylin and eosin stain; scale bar: 50 μm. (c) Scattered aggregates of lymphocytes expressing CD3 (arrowhead) are present multifocally. Immunohistochemical staining for CD3 with haematoxylin counterstain; scale bar: 100 μm. (d) Rarer individual lymphocytes expressing CD20 (arrowhead) are present between mammary alveoli. Immunohistochemical staining for CD20 with haematoxylin counterstain; scale bar: 100 μm. dL: days lactation

Fig. 2

Sub-gross anatomy and histology of the rabbit mammary gland. (a) Sub-gross histological section (sagittal plane) through the teat and mammary tissue of a wild rabbit, Oryctolagus cuniculus, during late pregnancy, estimated 27 dG. Multiple ducts (*) are apparent and exhibit dilatations suggestive of sinusoidal structures (S). (b) Transverse section of a rabbit teat canal, < 1 mm from the teat orifice, demonstrating the keratinized stratified squamous epithelium. (c) Transverse section of a mammary duct demonstrating the bilaminar epithelial lining (double headed arrow). (d) Mammary alveoli formed by a luminal layer of mammary epithelial cells and an underlying layer of myoepithelium. Haematoxylin and eosin stain; dG: days gestation

Fig. 3

Structural defences of the bovine mammary gland. Sagittal section through the distal gland cistern, teat cistern and teat canal of a periparturient Holstein Friesian dairy cow; formalin fixed tissue; scale bar: 10 mm. Teat cistern immunohistochemical inset: Sagittal section through the teat cistern. Scattered intraepithelial lymphocytes expressing CD3 are present multifocally. Immunohistochemical staining for CD3 with haematoxylin counterstain. Fürstenberg’s rosette histological inset: Sagittal section through the teat canal (TC) – distal teat cistern (diamond) junction, Fürstenberg’s rosette (*) of a Holstein Friesian dairy cow 45 dI. Groupings of small to moderate numbers of lymphocytes (L) are present multifocally. Haematoxylin and eosin stain; dI: days involution, with concurrent pregnancy until abortion at approximately 31dI

Fig. 4

Near- and far- stromal regions of the immature ovine mammary gland. Histolological section from the mammary gland of a nulliparous 18-month-old ewe lamb. Near-stromal regions (N) are within approximately 75 μm of mammary epithelial structures. Far-stromal regions (F) comprise both collagen rich connective tissue and adipose. Haematoxylin and eosin stain; scale bar: 50 μm