Visualizing the spatial organization of monocytes, interstitial macrophages, and tissue-specific macrophages in situ.

Tissue-resident mononuclear phagocytes (MPs) are an abundant cell population whose localization in situ reflects their identity. To enable assessment of their heterogeneity, we developed the red/green/blue (RGB)-Mac mouse based upon combinations of Cx3cr1 and Csf1r reporter transgenes, providing a complete visualization of their spatial organization in situ. 3D-multi-photon imaging for spatial mapping and spectral cytometry employing the three markers in combination distinguished tissue-associated monocytes, tissue-specific macrophages, and three subsets of connective-tissue-associated MPs, including CCR2 monocyte-derived cell, CX3CR1, and FOLR2 interstitial subsets, associated with distinct sub-anatomic territories.

Loss of embryonically-derived Kupffer cells during hypercholesterolemia accelerates atherosclerosis development.

Hypercholesterolemia is a major risk factor for atherosclerosis and associated cardiovascular diseases. The liver plays a key role in the regulation of plasma cholesterol levels and hosts a large population of tissue-resident macrophages known as Kupffer cells (KCs). KCs are located in the hepatic sinusoids where they ensure key functions including blood immune surveillance.

Tumor-associated macrophage heterogeneity is driven by tissue territories in breast cancer.

Tissue-resident macrophages adapt to local signals within tissues to acquire specific functions. Neoplasia transforms the tissue, raising the question as to how the environmental perturbations contribute to tumor-associated macrophage (TAM) identity and functions. Combining single-cell RNA sequencing (scRNA-seq) with spatial localization of distinct TAM subsets by imaging, we discover that TAM transcriptomic programs follow two main differentiation paths according to their localization in the stroma or in the neoplastic epithelium of the mammary duct.

Two New Neutrophil Subsets Define a Discriminating Sepsis Signature.

Sepsis is the leading cause of death in adult ICUs. At present, sepsis diagnosis relies on nonspecific clinical features. It could transform clinical care to have immune-cell biomarkers that could predict sepsis diagnosis and guide treatment.

LOX-1-Expressing Immature Neutrophils Identify Critically-Ill COVID-19 Patients at Risk of Thrombotic Complications.

Background: Lymphopenia and the neutrophil/lymphocyte ratio may have prognostic value in COVID-19 severity.

Objective: We investigated neutrophil subsets and functions in blood and bronchoalveolar lavage (BAL) of COVID-19 patients on the basis of patients' clinical characteristics.

Methods: We used a multiparametric cytometry profiling based to mature and immature neutrophil markers in 146 critical or severe COVID-19 patients.

Early activation of the cardiac CX3CL1/CX3CR1 axis delays β-adrenergic-induced heart failure.

We recently highlighted a novel potential protective paracrine role of cardiac myeloid CD11b/c cells improving resistance of adult hypertrophied cardiomyocytes to oxidative stress and potentially delaying evolution towards heart failure (HF) in response to early β-adrenergic stimulation. Here we characterized macrophages (Mφ) in hearts early infused with isoproterenol as compared to control and failing hearts and evaluated the role of upregulated CX3CL1 in cardiac remodeling. Flow cytometry, immunohistology and Mφ-depletion experiments evidenced a transient increase in Mφ number in isoproterenol-infused hearts, proportional to early concentric hypertrophy (ECH) remodeling and limiting HF.

TREM-1 orchestrates angiotensin II-induced monocyte trafficking and promotes experimental abdominal aortic aneurysm.

The triggering receptor expressed on myeloid cells 1 (TREM-1) drives inflammatory responses in several cardiovascular diseases but its role in abdominal aortic aneurysm (AAA) remains unknown. Our objective was to explore the role of TREM-1 in a mouse model of angiotensin II-induced (AngII-induced) AAA. TREM-1 expression was detected in mouse aortic aneurysm and colocalized with macrophages.

Publisher Correction: Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer.

Hormone receptor (HR) breast cancer (BC) causes most BC-related deaths, calling for improved therapeutic approaches. Despite expectations, immune checkpoint blockers (ICBs) are poorly active in patients with HR BC, in part reflecting the lack of preclinical models that recapitulate disease progression in immunocompetent hosts. We demonstrate that mammary tumors driven by medroxyprogesterone acetate (M) and 7,12-dimethylbenz[a]anthracene (D) recapitulate several key features of human luminal B HRHER2 BC, including limited immune infiltration and poor sensitivity to ICBs.

Revising CX3CR1 Expression on Murine Classical and Non-classical Monocytes.

In mice, monocytes (Mo) are conventionally described as CX3CR1 classical Mo (CMo) and CX3CR1 non-classical Mo (NCMo) based on the expression of EGFP in Cx3cr1 mice and by analogy with human CX3CR1 expression. Although this terminology is widely used, it may not reflect the expression of CX3CR1 on Mo subsets. Using an unsupervised multiparametric analysis of blood Mo in steady state and after sterile peritonitis, we observed that CX3CR1 expression did not discriminate the CMo from the NCMo subsets.

Impaired Kupffer Cell Self-Renewal Alters the Liver Response to Lipid Overload during Non-alcoholic Steatohepatitis.

Kupffer cells (KCs) are liver-resident macrophages that self-renew by proliferation in the adult independently from monocytes. However, how they are maintained during non-alcoholic steatohepatitis (NASH) remains ill defined. We found that a fraction of KCs derived from Ly-6C monocytes during NASH, underlying impaired KC self-renewal.

Sepsis Triggers a Late Expansion of Functionally Impaired Tissue-Vascular Inflammatory Monocytes During Clinical Recovery.

Sepsis is characterized by a systemic inflammation that can cause an immune dysfunction, for which the underlying mechanisms are unclear. We investigated the impact of cecal ligature and puncture (CLP)-mediated polymicrobial sepsis on monocyte (Mo) mobilization and functions. Our results show that CLP led to two consecutive phases of Mo deployment.

Phagocytosis of Wnt inhibitor SFRP4 by late wound macrophages drives chronic Wnt activity for fibrotic skin healing.

Human and murine skin wounding commonly results in fibrotic scarring, but the murine wounding model wound-induced hair neogenesis (WIHN) can frequently result in a regenerative repair response. Here, we show in single-cell RNA sequencing comparisons of semi-regenerative and fibrotic WIHN wounds, increased expression of phagocytic/lysosomal genes in macrophages associated with predominance of fibrotic myofibroblasts in fibrotic wounds. Investigation revealed that macrophages in the late wound drive fibrosis by phagocytizing dermal Wnt inhibitor SFRP4 to establish persistent Wnt activity.

Ontogeny of Tumor-Associated Macrophages.

Tumor-associated macrophages (TAM) represent the main immune cell population of the tumor microenvironment in most cancer. For decades, TAM have been the focus of intense investigation to understand how they modulate the tumor microenvironment and their implication in therapy failure. One consensus is that TAM are considered to exclusively originate from circulating monocyte precursors released from the bone marrow, fitting the original dogma of tissue-resident macrophage ontogeny.

Tracking Monocytes and Macrophages in Tumors With Live Imaging.

In most cancers, myeloid cells represent the major component of the immune microenvironment. Deciphering the impact of these cells on tumor growth and in response to various anti-tumor therapies is a key issue. Many studies have elucidated the role of tumor-associated monocytes and tumor-associated macrophages (TAM) in tumor development, angiogenesis, and therapeutic failure.

Ibrutinib induces multiple functional defects in the neutrophil response against .

The Bruton tyrosine kinase inhibitor ibrutinib has become a leading therapy against chronic lymphoid leukemia. Recently, ibrutinib has been associated with the occurrence of invasive fungal infections, in particular invasive aspergillosis. The mechanisms underlying the increased susceptibility to fungal infections associated with exposure to ibrutinib are currently unknown.

CCR2-Dependent Recruitment of Tregs and Monocytes Following Radiotherapy Is Associated with TNFα-Mediated Resistance.

Radiotherapy (RT) represents one of the main anticancer approaches for the treatment of solid tumors. Beyond the expected direct effects of RT on tumor cells, evidence supporting the importance of an immune response to RT is growing. The balance between RT-mediated immunogenic and tolerogenic activity is ill-defined and deserves more attention.

Macrophages of distinct origins contribute to tumor development in the lung.

Tissue-resident macrophages can self-maintain without contribution of adult hematopoiesis. Herein we show that tissue-resident interstitial macrophages (Res-TAMs) in mouse lungs contribute to the pool of tumor-associated macrophages (TAMs) together with CCR2-dependent recruited macrophages (MoD-TAMs). Res-TAMs largely correlated with tumor cell growth in vivo, while MoD-TAMs accumulation was associated with enhanced tumor spreading.

CSF1R inhibition prevents radiation pulmonary fibrosis by depletion of interstitial macrophages.

Radiation-induced lung fibrosis (RIF) is a delayed side-effect of chest radiotherapy, frequently associated with macrophage infiltration.We aimed to characterise the role of pulmonary macrophages in RIF using human lung biopsies from patients receiving radiotherapy for thorax malignancies and a RIF model developed in C57BL/6 mice after 16-Gy thorax irradiation.High numbers of macrophages (both interstitial and alveolar) were detected in clinical and preclinical RIF.