Developing ovine mammary terminal duct lobular units have a dynamic mucosal and stromal immune microenvironment

Nagy, Dorottya; Gillis, Clare M. C.; Davies, Katie; Fowden, Abigail L.; Rees, Paul; Wills, John W.; Hughes, Katherine

doi:10.1038/s42003-021-02502-6

Cited by 16 publications

(20 citation statements)

References 58 publications

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“…Most of the cells had the morphological appearance of macrophages. Macrophages (ionized calcium binding adaptor molecule 1 IBA1 pos cells) have been found in the ductal epithelium of pre-pregnancy lambs with increased density with age ( 45 ). Infusion of formalin-killed S. uberis increased the cellular expression of class II antigen both in connective tissue and in the epithelium lining the ducts and particularly the gland cistern.…”

Section: The Mammary Gland As An Immune Inductive Sitementioning

confidence: 99%

“…The role of the rosette formation in the defense of the MG remains to be defined. Intriguingly, lymphocyte aggregates resembling tertiary lymphoid follicles have been found in the MG of neonatal and 5–9.5 month-old lambs ( 45 ). These formations in the stroma adjacent to the mammary epithelium exhibit the typical arrangement of central B cells surrounded by T cells, in association with high endothelial venules expressing the vascular addressin PNAd.…”

Section: The Mammary Gland As An Immune Inductive Sitementioning

confidence: 99%

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Adaptive Cell-Mediated Immunity in the Mammary Gland of Dairy Ruminants

2022

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Mastitis is one of the greatest issues for the global dairy industry and controlling these infections by vaccination is a long-sought ambition that has remained unfulfilled so far. In fact, gaps in knowledge of cell-mediated immunity in the mammary gland (MG) have hampered progress in the rational design of immunization strategies targeting this organ, as current mastitis vaccines are unable to elicit a strong protective immunity. The objectives of this article are, from a comprehensive and critical review of available literature, to identify what characterizes adaptive immunity in the MG of ruminants, and to derive from this analysis research directions for the design of an optimal vaccination strategy. A peculiarity of the MG of ruminants is that it does not belong to the common mucosal immune system that links the gut immune system to the MG of rodents, swine or humans. Indeed, the MG of ruminants is not seeded by lymphocytes educated in mucosal epithelia of the digestive or respiratory tracts, because the mammary tissue does not express the vascular addressins and chemokines that would allow the homing of memory T cells. However, it is possible to elicit an adaptive immune response in the MG of ruminants by local immunization because the mammary tissue is provided with antigen-presenting cells and is linked to systemic mechanisms. The optimal immune response is obtained by luminal exposure to antigens in a non-lactating MG. The mammary gland can be sensitized to antigens so that a local recall elicits neutrophilic inflammation and enhanced defenses locally, resulting from the activation of resident memory lymphocytes producing IFN-γ and/or IL-17 in the mammary tissue. The rational exploitation of this immunity by vaccination will need a better understanding of MG cell-mediated immunity. The phenotypic and functional characterization of mammary antigen-presenting cells and memory T cells are amongst research priorities. Based on current knowledge, rekindling research on the immune cells that populate the healthy, infected, or immunized MG appears to be a most promising approach to designing efficacious mastitis vaccines.

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Section: The Mammary Gland As An Immune Inductive Sitementioning

confidence: 99%

Section: The Mammary Gland As An Immune Inductive Sitementioning

confidence: 99%

Adaptive Cell-Mediated Immunity in the Mammary Gland of Dairy Ruminants

2022

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“…The aggregation of lymphocytes, such as TLOs, has been observed in the mammary glands of ruminants ( 20 – 22 ). However, the feature or stage of these TLOs, the production of immunoglobulins and their interaction with other antimicrobial components, and the properties of TJs in mammary epithelial cells near the TLOs remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Investigating mammary glands of lactating goats for the presence of tertiary lymphoid organs

et al. 2022

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Ectopic tertiary lymphoid organs (TLOs) have been identified in many organs, such as the lungs, nasal cavities, and kidneys of both mice and humans. Although lymphocyte aggregates have been observed in the mammary glands of ruminants, the details remain unclear. In this study, we investigated the mammary glands of lactating goats for the presence of TLOs. The localization of CD20 (B cells), CD3 (T cells), MECA79 (high endothelial venules), CD40 (follicular dendritic cells), BCL6 (germinal center), and IgA was examined by immunohistochemistry. The concentrations of IgG, IgA, lactoferrin, β-defensin-1, cathelicidin-2, cathelicidin-7, S100A7, and S100A8 in milk were measured by ELISA. The localization and amount of tight junction (TJ) proteins (claudin-3 and claudin-4) were examined using immunofluorescence and western blotting. We found that 19 out of 30 udders contained lymphocyte aggregates, which showed positive reactions against CD20, CD3, CD40, and MECA79. In addition, large-sized aggregations showed separate localization of B cells and T cells and a positive reaction against BCL6, although BCL6 was sparsely localized in the aggregations. These results indicate that mammary glands of lactating goats contain TLOs. The IgG and IgA concentrations in the milk of TLO-positive goats and the number of IgA-positive cells were higher than those in negative goats. Furthermore, claudin-4 was localized in the TJ region and the amount was higher in TLO-positive mammary glands than that in the negative group, indicating the presence of leakages at TJs. In conclusion, a majority of lactating goat udders have TLOs, which contribute to local immunity by producing immunoglobulins.

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“…Convolutional neural networks have been applied to detect mitotic activity from histological slides of canine cancers 13,29 . In sheep, deep learning has been employed to delineate growth phases of mammary development 30 . Other machine learning techniques have been used to classify a common gastrointestinal disease in cats 31 .…”

Section: Introductionmentioning

confidence: 99%

AI-powered pan-species computational pathology: bridging clinic and wildlife care

AbdulJabbar

Castillo

Hughes

et al. 2022

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Cancers occur across species. Understanding what is consistent and varies across species can provide new insights into cancer initiation and evolution, with significant implications for animal welfare and wildlife conservation. We built the pan-species cancer digital pathology atlas (PANCAD) and conducted the first pan-species study of computational comparative pathology using a supervised convolutional neural network algorithm trained on human samples. The artificial intelligence algorithm achieves high accuracy in measuring immune response through single-cell classification for two transmissible cancers (canine transmissible venereal tumour, 0.94; Tasmanian devil facial tumour disease, 0.88). Furthermore, in 18 other vertebrate species (mammalia=11, reptilia=4, aves=2, and amphibia=1), accuracy (0.57-0.94) was influenced by cell morphological similarity preserved across different taxonomic groups, tumour sites, and variations in the immune compartment. A new metric, named morphospace overlap, was developed to guide veterinary pathologists towards rational deployment of this technology on new samples. This study provides the foundation and guidelines for transferring artificial intelligence technologies to veterinary pathology based on a new understanding of morphological conservation, which could vastly accelerate new developments in veterinary medicine and comparative oncology.

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Developing ovine mammary terminal duct lobular units have a dynamic mucosal and stromal immune microenvironment

Cited by 16 publications

References 58 publications

Adaptive Cell-Mediated Immunity in the Mammary Gland of Dairy Ruminants

Adaptive Cell-Mediated Immunity in the Mammary Gland of Dairy Ruminants

Investigating mammary glands of lactating goats for the presence of tertiary lymphoid organs

AI-powered pan-species computational pathology: bridging clinic and wildlife care

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