Barrier-tissue macrophages: functional adaptation to environmental challenges

Mowat, A M; Scott, Charlotte; Bain, Calum C.

doi:10.1038/nm.4430

Cited by 125 publications

(121 citation statements)

References 186 publications

(255 reference statements)

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“…Intestinal macrophages in mice are heterogeneous and arise from the CCR2-dependent replenishment by blood classical monocytes (Bain et al, 2014) and from embryonic precursors that are recruited to the intestine prior birth (De Schepper et al, 2018). In the healthy intestine, tissue resident macrophages are epigenetically wired by local microenvironmental cues to acquire a regulatory program necessary for the establishment and preservation of intestinal homeostasis (Lavin et al, 2014; Mowat et al, 2017). Part of this program comprises the acquisition of inhibitory mechanisms limiting the production of inflammatory cytokines in response to inflammatory stimuli by gut-resident macrophages (Smythies et al, 2005, 2010).…”

Section: Discussionmentioning

confidence: 99%

Single-cell analysis of Crohn’s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy

Martin

Boschetti

Chang

et al. 2018

Preprint

106

226

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Clinical benefits to cytokine blockade in ileal Crohn's disease (iCD) have been limited to a subset of patients. Whether cellular and molecular heterogeneity contributes to variability in treatment responses has been unclear. Using single cell technologies combining scRNAseq, CyTOF and multiplex tissue imaging, we mapped the cellular landscape of inflamed ileum lesions, adjacent non-inflamed ileum and matched circulating blood cells of iCD patients.In inflamed tissues, we identified a pathogenic module characterized by an inflammatory mononuclear phagocyte (Inf.MNP)-associated cellular response organized around inflammatory macrophages and mature dendritic cells in a subset of iCD patients. We confirmed the Inf.MNPassociated cellular response in 4 independent iCD cohorts (n=441) and showed that presence of this pathogenic module at diagnosis correlated with primary resistance to anti-TNF therapy.Single cell mapping of iCD tissues identifies a complex cellular signature of anti-TNF resistance thereby revealing novel biomarkers of treatment response and tailored therapeutic opportunities.

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Section: Discussionmentioning

confidence: 99%

Single-cell analysis of Crohn’s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy

Martin

Boschetti

Chang

et al. 2018

Preprint

106

226

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“…23,29,30 Lastly, in the skin, macrophages might be present as Langerhans cells or histiocytes, which primarily function in phagocytosis as well as antigen capture, processing, and presentation. 13,[21][22][23][31][32][33]…”

Section: Introductionmentioning

confidence: 99%

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

Sousa¹,

Vasconcelos²,

Quaresma³

2019

IDR

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Macrophages are a functionally heterogeneous group of cells with specialized functions depending not only on their subgroup but also on the function of the organ or tissue in which the cells are located. The concept of macrophage phenotypic heterogeneity has been investigated since the 1980s, and more recent studies have identified a diverse spectrum of phenotypic subpopulations. Several types of macrophages play a central role in the response to infectious agents and, along with other components of the immune system, determine the clinical outcome of major infectious diseases. Here, we review the functions of various macrophage phenotypic subpopulations, the concept of macrophage polarization, and the influence of these cells on the evolution of infections. In addition, we emphasize their role in the immune response in vivo and in situ, as well as the molecular effectors and signaling mechanisms used by these cells. Furthermore, we highlight the mechanisms of immune evasion triggered by infectious agents to counter the actions of macrophages and their consequences. Our aim here is to provide an overview of the role of macrophages in the pathogenesis of critical transmissible diseases and discuss how elucidation of this relationship could enhance our understanding of the host–pathogen association in organ-specific immune responses.

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“…Macrophages in barrier tissues, such as the intestine, lung, skin and urinary bladder, are constantly exposed to environmental cues of the outside world and replenished by invading monocytes during health, inflammation and resolution (Mowat et al, 2017). The differentiation into macrophages is shaped by the tissue microenvironment and migratory and functional adaptations of macrophages are critical to respond to the needs of the anatomical niche.…”

Section: Discussionmentioning

confidence: 99%

Relocation of macrophages maintains the barrier function of the urothelium and protects against persistent infection

Bottek

Soun

Volke

et al. 2019

Preprint

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Macrophages perform essential functions during bacterial infections, such as phagocytosis of pathogens and elimination of neutrophils to reduce spreading of infection, inflammation and tissue damage. The spatial distribution of macrophages is critical to respond to tissue specific adaptations upon infections. Using a novel algorithm for correlative mass spectrometry imaging and state-of-the-art multiplex microscopy, we report here that macrophages within the urinary bladder are positioned in the connective tissue underneath the urothelium. Invading uropathogenic E.coli induced an IL-6-dependent CX 3 CL1 expression by urothelial cells, facilitating relocation of macrophages from the connective tissue into the urothelium. These cells phagocytosed UPECs and eliminated neutrophils to maintain barrier function of the urothelium, preventing persistent and recurrent urinary tract infection. Bottek et al., 2019 Macrophages maintain barrier function GRAPHICAL ABSTRACT

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Barrier-tissue macrophages: functional adaptation to environmental challenges

Cited by 125 publications

References 186 publications

Single-cell analysis of Crohn’s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy

Single-cell analysis of Crohn’s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

Relocation of macrophages maintains the barrier function of the urothelium and protects against persistent infection

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