Dataset Information

Distinct lactation-associated macrophages exist in murine mammary tissue and human milk

ABSTRACT: Macrophages are involved in immune defense, organogenesis and tissue homeostasis. They also contribute to the different phases of mammary gland remodeling during development, pregnancy and involution post-lactation. Yet, less is known about the dynamics of mammary gland macrophages in the lactation stage. Here, we describe a macrophage population present during lactation in mice. By multi-parameter flow cytometry and single-cell RNA sequencing we reveal this population as distinct from the two resident macrophage subsets present pregestationally. These lactation-induced macrophages (LiMacs) are predominantly monocyte-derived and expand by proliferation in situ concomitant with nursing. LiMacs develop independently of IL-34 but require CSF-1 signaling and are partly microbiota-dependent. Locally, they reside adjacent to the basal cells of the alveoli and extravasate into the milk. Moreover, we also found several macrophage subsets in human milk, resembling LiMacs. Collectively, these findings reveal the emergence of unique macrophages in the mammary gland and milk during lactation.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Milk

SUBMITTER: Ekaterina Petrova

LAB HEAD: Melanie Greter

PROVIDER: PXD041711 | Pride | 2023-06-23

REPOSITORIES: Pride

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Publications

Lactation-associated macrophages exist in murine mammary tissue and human milk.

Cansever Dilay D Petrova Ekaterina E Krishnarajah Sinduya S Mussak Caroline C Welsh Christina A CA Mildenberger Wiebke W Mulder Kevin K Kreiner Victor V Roussel Elsa E Stifter Sebastian A SA Andreadou Myrto M Zwicky Pascale P Jurado Nicole Puertas NP Rehrauer Hubert H Tan Ge G Liu Zhaoyuan Z Blériot Camille C Ronchi Francesca F Macpherson Andrew J AJ Ginhoux Florent F Natalucci Giancarlo G Becher Burkhard B Greter Melanie M

Nature immunology 20230619 7

Macrophages are involved in immune defense, organogenesis and tissue homeostasis. Macrophages contribute to the different phases of mammary gland remodeling during development, pregnancy and involution postlactation. Less is known about the dynamics of mammary gland macrophages in the lactation stage. Here, we describe a macrophage population present during lactation in mice. By multiparameter flow cytometry and single-cell RNA sequencing, we identified a lactation-induced CD11c<sup>+</sup>CX3CR ...[more]

PMID: 37337103

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Project description:Production of milk is a key characteristic of mammals, but the features of lactation vary greatly between monotreme, marsupial and eutherian mammals. Marsupials have a short gestation followed by a long lactation period, and the milk constituents vary greatly across lactation to meet the changing needs of the developing young. Marsupials are born immunologically naïve and rely on their mother’s milk for immunological protection. The koala is an iconic Australian species and many are increasingly threatened by disease. Here we use a mammary transcriptome, two milk proteomes and the koala genome to comprehensively characterise the protein components of the milk of the koala, with a key focus on the immune constituents during early and late lactation. We have characterised the most abundant peptides present in milk, examined key differences between early and late lactation, and determined differences between the koala and other marsupial species. The most abundant proteins were well characterised mammalian and marsupial-specific milk proteins including β-lactoglobulin, lactotransferrin, caseins and early lactation protein. We have generated a list of 851 immune compounds identified in the mammary transcriptome and examined a range of immune proteins that were highly abundant in the milk proteomes. These include immunoglobulins, complement components and immune receptors. A host of antimicrobial peptides were identified including cathelicidins, lysozyme, WAP four-disulfide core domain protein 2, Mucin-1 and Peptidoglycan recognition protein. We discovered that the previously described marsupial milk protein Very Early Lactation Protein is an ortholog of the eutherian gene Glycam1 (PP3) and likely has an antimicrobial role in milk. We also identified highly abundant koala endogenous retrovirus sequences in the mammary and milk transcriptome and proteomes, identifying a potential route for retroviral transmission from mother to young. Identifying and characterising the immune components of milk is key to understanding how marsupial young are protected throughout lactation and the novel immune compounds identified may have applications in clinical research.

Dataset Information

Distinct lactation-associated macrophages exist in murine mammary tissue and human milk

Publications

Lactation-associated macrophages exist in murine mammary tissue and human milk.

Similar Datasets

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