Intestinal Mononuclear Phagocytes in Health and Disease

Author(s):  
Massimo Locati ◽  
Graziella Curtale ◽  
Alberto Mantovani

Macrophages are a diverse set of cells present in all body compartments. This diversity is imprinted by their ontogenetic origin (embryonal versus adult bone marrow–derived cells); the organ context; by their activation or deactivation by various signals in the contexts of microbial invasion, tissue damage, and metabolic derangement; and by polarization of adaptive T cell responses. Classic adaptive responses of macrophages include tolerance, priming, and a wide spectrum of activation states, including M1, M2, or M2-like. Moreover, macrophages can retain long-term imprinting of microbial encounters (trained innate immunity). Single-cell analysis of mononuclear phagocytes in health and disease has added a new dimension to our understanding of the diversity of macrophage differentiation and activation. Epigenetic landscapes, transcription factors, and microRNA networks underlie the adaptability of macrophages to different environmental cues. Macrophage plasticity, an essential component of chronic inflammation, and its involvement in diverse human diseases, most notably cancer, is discussed here as a paradigm.


2017 ◽  
pp. 687-700
Author(s):  
Theodore J. Sanders ◽  
Ulf Yrlid ◽  
Kevin J. Maloy

2020 ◽  
Author(s):  
Joshua M. Peters ◽  
Paul C. Blainey ◽  
Bryan D. Bryson

SUMMARYMonocytes, dendritic cells, and macrophages, commonly referred to as mononuclear phagocytes (MNPs), are innate immune cells capable of adopting diverse homeostatic and pathogenic phenotypes. Recent single-cell RNA-sequencing studies across many diseases in the lung have profiled this diversity transcriptionally, defining new cellular states and their association with disease. Despite these massive cellular profiling efforts, many studies have focused on defining myeloid dysfunction in specific diseases without identifying common pan-disease trends in the mononuclear phagocyte compartment within the lung. To address these gaps in our knowledge, we collate, process, and analyze 561,390 cellular transcriptomes from 12 studies of the human lung across multiple human diseases. We develop a computational framework to identify and compare dominant gene markers and gene expression programs and characterize MNP diversity in the lung, proposing a conserved dictionary of gene sets. Utilizing this reference, we efficiently identify disease-associated and rare MNP populations across multiple diseases and cohorts. Furthermore, we demonstrate the utility of this dictionary in characterizing a recently published dataset of bronchoalveolar lavage cells from COVID-19 patients and healthy controls which further reveal novel transcriptional shifts directly relatable to other diseases in the lung. These results underline conserved MNP transcriptional programs in lung disease, provide an immediate reference for characterizing the landscape of lung MNPs and establish a roadmap to dissecting MNP transcriptional complexity across tissues.


2021 ◽  
pp. 002203452110048
Author(s):  
H. Sharawi ◽  
O. Heyman ◽  
G. Mizraji ◽  
Y. Horev ◽  
A. Laviv ◽  
...  

As the most potent cells activating and polarizing naive T cells, dendritic cells (DCs) are of major importance in the induction of immunity and tolerance. DCs are a heterogeneous population of antigen-presenting cells that are widely distributed in lymphoid and nonlymphoid tissues. Murine studies have highlighted the important role of oral DCs and Langerhans cells (LCs) in orchestrating the physiological homeostasis of the oral mucosa. DCs are also critically involved in pathological conditions such as periodontal diseases, in which gingival DCs appear to have special localization and function. While the characterization of human DCs in health and disease has been extensively investigated in various tissues, this topic was rarely studied in human gingiva. Here, we employed an up-to-date approach to characterize by flow cytometry the gingival DCs of 27 healthy subjects and 21 periodontal patients. Four distinct subsets of mononuclear phagocytes were identified in healthy gingiva: conventional DC type 1 (cDC1), cDC2, plasmacytoid DCs (pDCs), and LCs. In periodontitis patients, the frequencies of gingival LCs and pDCs were dysregulated, as LCs decreased, whereas pDCs increased in the diseased gingiva. This shift in the prevalence of DCs was accompanied by increased expression of the proinflammatory cytokines interleukin (IL)–1β, interferon (IFN)–α, and IFN-γ, while the anti-inflammatory cytokine IL-10 was suppressed. We further found that smoking, a known risk factor of periodontitis, specifically reduces gingival LCs in healthy individuals, indicating a possible role of LCs in the elevated severity of periodontitis in smokers. Collectively, this work reveals the various DC subsets residing in the human gingiva and the impact of periodontitis, as well as smoking, on the prevalence of each subset. Our findings provide a foundation toward understanding the role of human DCs in orchestrating physiological oral immunity and set the stage for the evaluation and modulation of shifts in immunity associated with periodontitis.


2020 ◽  
Vol 217 (3) ◽  
Author(s):  
Iva Lelios ◽  
Dilay Cansever ◽  
Sebastian G. Utz ◽  
Wiebke Mildenberger ◽  
Sebastian A. Stifter ◽  
...  

Macrophages are part of the innate immune system and are present in every organ of the body. They fulfill critical roles in tissue homeostasis and development and are involved in various pathologies. An essential factor for the development, homeostasis, and function of mononuclear phagocytes is the colony stimulating factor-1 receptor (CSF-1R), which has two known ligands: CSF-1 and interleukin-34 (IL-34). While CSF-1 has been extensively studied, the biology and functions of IL-34 are only now beginning to be uncovered. In this review, we discuss recent advances of IL-34 biology in health and disease with a specific focus on mononuclear phagocytes.


2020 ◽  
Vol 40 (1_suppl) ◽  
pp. S134-S136 ◽  
Author(s):  
Xiaoming Hu

Microglia and non-parenchymal macrophages are increasingly recognized to play critical roles in the central nervous system (CNS) health and disease. Accumulating evidence suggests that these mononuclear phagocytes do not constitute stereotypical cell populations, but rather polarize into a variety of phenotypes at different stages of CNS development, stresses, and diseases. This commentary aims to discuss our current consensus and controversy on microglia/macrophage phenotypes. Collective single-cell level evidence validates the concept of microglia/macrophage polarization, while suggests multi-polarity instead of dichotomic polarization. Characterizing the functions of a specific microglia/macrophage phenotype is challenging yet essential to translate our scientific discoveries into clinical application.


mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Soo Chan Lee

ABSTRACT Soo Chan Lee works in the field of medical mycology. In this mSphere of Influence article, he reflects on how “Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis” (Science 336:1314–1317, 2012, https://doi.org/10.1126/science.1221789) by I. D. Iliev, V. A. Funari, K. D. Taylor, Q. Nguyen, et al., “CX3CR1+ mononuclear phagocytes control immunity to intestinal fungi” (Science 359:232–236, 2018, https://doi.org/10.1126/science.aao1503) by I. Leonardi, X. Li, A. Semon, D. Li, et al., and “The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL” (Nature 574:264–267, 2019, https://doi.org/10.1038/s41586-019-1608-2) by B. Aykut, S. Pushalkar, R. Chen, Q. Li, et al. made an impact on him to study medically important fungi by providing a forum to understand the roles of fungal microbiota or mycobiota in human diseases and health.


2017 ◽  
Vol 8 ◽  
Author(s):  
Faezzah Baharom ◽  
Gregory Rankin ◽  
Anders Blomberg ◽  
Anna Smed-Sörensen

Author(s):  
Sarah A. Luse

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.


Author(s):  
K. E. Muse ◽  
D. G. Fischer ◽  
H. S. Koren

Mononuclear phagocytes, a pluripotential cell line, manifest an array of basic extracellular functions. Among these physiological regulatory functions is the expression of spontaneous cytolytic potential against tumor cell targets.The limited observations on human cells, almost exclusively blood monocytes, initially reported limited or a lack of tumoricidal activity in the absence of antibody. More recently, freshly obtained monocytes have been reported to spontaneously impair the biability of tumor target cells in vitro (Harowitz et al., 1979; Montavani et al., 1979; Hammerstrom, 1979). Although the mechanism by which effector cells express cytotoxicity is poorly understood, discrete steps can be distinguished in the process of cell mediated cytotoxicity: recognition and binding of effector to target cells,a lethal-hit stage, and subsequent lysis of the target cell. Other important parameters in monocyte-mediated cytotoxicity include, activated state of the monocyte, effector cell concentrations, and target cell suseptibility. However, limited information is available with regard to the ultrastructural changes accompanying monocyte-mediated cytotoxicity.


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