scholarly journals GM-CSF: Orchestrating the Pulmonary Response to Infection

2022 ◽  
Vol 12 ◽  
Author(s):  
Thomas S. McCormick ◽  
Rana B. Hejal ◽  
Luis O. Leal ◽  
Mahmoud A. Ghannoum
Keyword(s):  
Infectious Diseases ◽  
Respiratory Infections ◽  
Critical Role ◽  
Alveolar Epithelium ◽  
Cell Types ◽  
Adjunctive Treatment ◽  
Gm Csf ◽  
Lung Physiology ◽  
Pulmonary Immune System ◽  
And Function

This review summarizes the structure and function of the alveolar unit, comprised of alveolar macrophage and epithelial cell types that work in tandem to respond to infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) helps to maintain the alveolar epithelium and pulmonary immune system under physiological conditions and plays a critical role in restoring homeostasis under pathologic conditions, including infection. Given the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and global spread of coronavirus disease 2019 (COVID-19), with subsequent acute respiratory distress syndrome, understanding basic lung physiology in infectious diseases is especially warranted. This review summarizes clinical and preclinical data for GM-CSF in respiratory infections, and the rationale for sargramostim (yeast-derived recombinant human [rhu] GM-CSF) as adjunctive treatment for COVID-19 and other pulmonary infectious diseases.

scholarly journals The lung–gut axis during viral respiratory infections: the impact of gut dysbiosis on secondary disease outcomes

2021 ◽  
Author(s):  
Valentin Sencio ◽  
Marina Gomes Machado ◽  
François Trottein
Keyword(s):  
Gut Microbiota ◽  
Bacterial Infections ◽  
Respiratory Infections ◽  
Critical Role ◽  
Good Health ◽  
Disease Outcomes ◽  
And Function ◽  
Viral Respiratory Infections ◽  
The Impact ◽  
Viral Respiratory

AbstractBacteria that colonize the human gastrointestinal tract are essential for good health. The gut microbiota has a critical role in pulmonary immunity and host’s defense against viral respiratory infections. The gut microbiota’s composition and function can be profoundly affected in many disease settings, including acute infections, and these changes can aggravate the severity of the disease. Here, we discuss mechanisms by which the gut microbiota arms the lung to control viral respiratory infections. We summarize the impact of viral respiratory infections on the gut microbiota and discuss the potential mechanisms leading to alterations of gut microbiota’s composition and functions. We also discuss the effects of gut microbial imbalance on disease outcomes, including gastrointestinal disorders and secondary bacterial infections. Lastly, we discuss the potential role of the lung–gut axis in coronavirus disease 2019.

Form and Function in Cells of the Brain

The Neuron ◽  
2015 ◽  
pp. 23-38
Author(s):  
Irwin B. Levitan ◽  
Leonard K. Kaczmarek
Keyword(s):  
Axonal Transport ◽  
Molecular Motors ◽  
Critical Role ◽  
Neuronal Cell ◽  
Cell Types ◽  
Neuronal Cell Body ◽  
Long Distance ◽  
Form And Function ◽  
And Function ◽  
The Brain

This chapter examines unique mechanisms that the neuron has evolved to establish and maintain the form required for its specialized signaling functions. Unlike some other organs, the brain contains a variety of cell types including several classes of glial cells, which play a critical role in the formation of the myelin sheath around axons and may be involved in immune responses, synaptic transmission, and long-distance calcium signaling in the brain. Neurons share many features in common with other cells (including glia), but they are distinguished by their highly asymmetrical shapes. The neuronal cytoskeleton is essential for establishing this cell shape during development and for maintaining it in adulthood. The process of axonal transport moves vesicles and other organelles to regions remote from the neuronal cell body. Proteins such as kinesin and dynein, called molecular motors, make use of the energy released by hydrolysis of ATP to drive axonal transport.

scholarly journals Hypoxia. 4. Hypoxia and ion channel function

2011 ◽  
Vol 300 (5) ◽  
pp. C951-C967 ◽  
Author(s):  
Larissa A. Shimoda ◽  
Jan Polak
Keyword(s):  
Ion Channels ◽  
Cell Function ◽  
Critical Role ◽  
Cardiac Contractility ◽  
Cell Types ◽  
Cellular Processes ◽  
Oxygen Sensitive ◽  
Sense And Respond ◽  
And Function ◽  
And Control

The ability to sense and respond to oxygen deprivation is required for survival; thus, understanding the mechanisms by which changes in oxygen are linked to cell viability and function is of great importance. Ion channels play a critical role in regulating cell function in a wide variety of biological processes, including neuronal transmission, control of ventilation, cardiac contractility, and control of vasomotor tone. Since the 1988 discovery of oxygen-sensitive potassium channels in chemoreceptors, the effect of hypoxia on an assortment of ion channels has been studied in an array of cell types. In this review, we describe the effects of both acute and sustained hypoxia (continuous and intermittent) on mammalian ion channels in several tissues, the mode of action, and their contribution to diverse cellular processes.

scholarly journals Emerging concepts and future challenges in innate lymphoid cell biology

2016 ◽  
Vol 213 (11) ◽  
pp. 2229-2248 ◽  
Author(s):  
Elia D. Tait Wojno ◽  
David Artis
Keyword(s):  
Immune Cells ◽  
Cell Biology ◽  
Critical Role ◽  
Cell Types ◽  
Lymphoid Cells ◽  
Adaptive Immune Cells ◽  
New Findings ◽  
Basic Studies ◽  
New Treatments ◽  
And Function

Innate lymphoid cells (ILCs) are innate immune cells that are ubiquitously distributed in lymphoid and nonlymphoid tissues and enriched at mucosal and barrier surfaces. Three major ILC subsets are recognized in mice and humans. Each of these subsets interacts with innate and adaptive immune cells and integrates cues from the epithelium, the microbiota, and pathogens to regulate inflammation, immunity, tissue repair, and metabolic homeostasis. Although intense study has elucidated many aspects of ILC development, phenotype, and function, numerous challenges remain in the field of ILC biology. In particular, recent work has highlighted key new questions regarding how these cells communicate with their environment and other cell types during health and disease. This review summarizes new findings in this rapidly developing field that showcase the critical role ILCs play in directing immune responses through their ability to interact with a variety of hematopoietic and nonhematopoietic cells. In addition, we define remaining challenges and emerging questions facing the field. Finally, this review discusses the potential application of basic studies of ILC biology to the development of new treatments for human patients with inflammatory and infectious diseases in which ILCs play a role.

scholarly journals ABL kinase inhibition promotes lung regeneration through expansion of an SCGB1A1+ SPC+ cell population following bacterial pneumonia

2019 ◽  
Vol 116 (5) ◽  
pp. 1603-1612 ◽  
Author(s):  
Aaditya Khatri ◽  
Bryan D. Kraft ◽  
Purushothama Rao Tata ◽  
Scott H. Randell ◽  
Claude A. Piantadosi ◽  
...  
Keyword(s):  
Cell Population ◽  
Bacterial Pneumonia ◽  
Respiratory Infections ◽  
Alveolar Epithelium ◽  
Cell Types ◽  
Therapeutic Interventions ◽  
Alveolar Cells ◽  
Cellular Targets ◽  
Type Ii Alveolar Cells ◽  
Efficient Recovery

Current therapeutic interventions for the treatment of respiratory infections are hampered by the evolution of multidrug resistance in pathogens as well as the lack of effective cellular targets. Despite the identification of multiple region-specific lung progenitor cells, the identity of molecules that might be therapeutically targeted in response to infections to promote activation of progenitor cell types remains elusive. Here, we report that loss of Abl1 specifically in SCGB1A1-expressing cells leads to a significant increase in the proliferation and differentiation of bronchiolar epithelial cells, resulting in dramatic expansion of an SCGB1A1+ airway cell population that coexpresses SPC, a marker for type II alveolar cells that promotes alveolar regeneration following bacterial pneumonia. Furthermore, treatment with an Abl-specific allosteric inhibitor enhanced regeneration of the alveolar epithelium and promoted accelerated recovery of mice following pneumonia. These data reveal a potential actionable target that may be exploited for efficient recovery after pathogen-induced infections.

scholarly journals Critical role for scaffolding adapter Gab2 in FcγR-mediated phagocytosis

2003 ◽  
Vol 161 (6) ◽  
pp. 1151-1161 ◽  
Author(s):  
Haihua Gu ◽  
Roberto J. Botelho ◽  
Min Yu ◽  
Sergio Grinstein ◽  
Benjamin G. Neel
Keyword(s):  
De Novo ◽  
Lipid Production ◽  
Critical Role ◽  
Cell Types ◽  
Regulatory Subunit ◽  
Pleckstrin Homology Domain ◽  
Downstream Target ◽  
Phosphoinositide 3 Kinase ◽  
And Function ◽  
Auxiliary Role

Grb2-associated binder 2 (Gab2), a member of the Dos/Gab subfamily scaffolding molecules, plays important roles in regulating the growth, differentiation, and function of many hematopoietic cell types. In this paper, we reveal a novel function of Gab2 in Fcγ receptor (FcγR)–initiated phagocytosis in macrophages. Upon FcγR activation, Gab2 becomes tyrosyl phosphorylated and associated with p85, the regulatory subunit of phosphoinositide 3-kinase (PI3K), and the protein–tyrosine phosphatidylinositol Shp-2. FcγR-mediated phagocytosis is severely impaired in bone marrow–derived macrophages from Gab2−/− mice. The defect in phagocytosis correlates with decreased FcγR-evoked activation of Akt, a downstream target of PI3K. Using confocal fluorescence microscopy, we find that Gab2 is recruited to the nascent phagosome, where de novo PI3K lipid production occurs. Gab2 recruitment requires the pleckstrin homology domain of Gab2 and is sensitive to treatment with the PI3K inhibitor wortmannin. The Grb2 binding site on Gab2 also plays an auxiliary role in recruitment to the phagosome. Because PI3K activity is required for FcγR-mediated phagocytosis, our results indicate that Gab2 acts as a key component of FcγR-mediated phagocytosis, most likely by amplifying PI3K signaling in the nascent phagosome.

scholarly journals Malaria Pigment Hemozoin Impairs GM-CSF Receptor Expression and Function by 4-Hydroxynonenal

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1259
Author(s):  
Oleksii Skorokhod ◽  
Valentina Barrera ◽  
Giorgia Mandili ◽  
Federica Costanza ◽  
Elena Valente ◽  
...  
Keyword(s):  
Direct Interaction ◽  
Cell Types ◽  
Receptor Expression ◽  
Amino Acid Residues ◽  
Gm Csf ◽  
Malaria Pigment ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
And Function

Malarial pigment hemozoin (HZ) generates the lipoperoxidation product 4-hydroxynonenal (4-HNE), which is known to cause dysregulation of the immune response in malaria. The inhibition of granulocyte macrophage colony-stimulating factor (GM-CSF)-dependent differentiation of dendritic cells (DC) by HZ and 4-HNE was previously described in vitro, and the GM-CSF receptor (GM-CSF R) was hypothesised to be a primary target of 4-HNE in monocytes. In this study, we show the functional impact of HZ on GM-CSF R in monocytes and monocyte-derived DC by (i) impairing GM-CSF binding by 50 ± 9% and 65 ± 14%, respectively (n = 3 for both cell types); (ii) decreasing the expression of GM-CSF R functional subunit (CD116) on monocyte’s surface by 36 ± 11% (n = 6) and in cell lysate by 58 ± 16% (n = 3); and (iii) binding of 4-HNE to distinct amino acid residues on CD116. The data suggest that defective DC differentiation in malaria is caused by GM-CSF R dysregulation and GM-CSF R modification by lipoperoxidation product 4-HNE via direct interaction with its CD116 subunit.

scholarly journals PPARgamma in Metabolism, Immunity, and Cancer: Unified and Diverse Mechanisms of Action

2021 ◽  
Vol 12 ◽  
Author(s):  
Miguel Hernandez-Quiles ◽  
Marjoleine F. Broekema ◽  
Eric Kalkhoven
Keyword(s):  
Regulatory Networks ◽  
Target Gene ◽  
Critical Role ◽  
Tumor Development ◽  
Cell Types ◽  
Mechanisms Of Action ◽  
Loss Of Function ◽  
Treatment Of Obesity ◽  
And Function ◽  
Cancer And Inflammation

The proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily, is one of the most extensively studied ligand-inducible transcription factors. Since its identification in the early 1990s, PPARγ is best known for its critical role in adipocyte differentiation, maintenance, and function. Emerging evidence indicates that PPARγ is also important for the maturation and function of various immune system-related cell types, such as monocytes/macrophages, dendritic cells, and lymphocytes. Furthermore, PPARγ controls cell proliferation in various other tissues and organs, including colon, breast, prostate, and bladder, and dysregulation of PPARγ signaling is linked to tumor development in these organs. Recent studies have shed new light on PPARγ (dys)function in these three biological settings, showing unified and diverse mechanisms of action. Classical transactivation—where PPARγ activates genes upon binding to PPAR response elements as a heterodimer with RXRα—is important in all three settings, as underscored by natural loss-of-function mutations in FPLD3 and loss- and gain-of-function mutations in tumors. Transrepression—where PPARγ alters gene expression independent of DNA binding—is particularly relevant in immune cells. Interestingly, gene translocations resulting in fusion of PPARγ with other gene products, which are unique to specific carcinomas, present a third mode of action, as they potentially alter PPARγ’s target gene profile. Improved understanding of the molecular mechanism underlying PPARγ activity in the complex regulatory networks in metabolism, cancer, and inflammation may help to define novel potential therapeutic strategies for prevention and treatment of obesity, diabetes, or cancer.

scholarly journals Phosphoinositide lipids in primary cilia biology

2020 ◽  
Vol 477 (18) ◽  
pp. 3541-3565
Author(s):  
Sarah E. Conduit ◽  
Bart Vanhaesebroeck
Keyword(s):  
Primary Cilia ◽  
Critical Role ◽  
Phospholipid Composition ◽  
Cell Types ◽  
Phosphoinositide Metabolism ◽  
Lipid Phosphatases ◽  
Regulatory Enzymes ◽  
Lipid Species ◽  
Cilia Formation ◽  
And Function

Primary cilia are solitary signalling organelles projecting from the surface of most cell types. Although the ciliary membrane is continuous with the plasma membrane it exhibits a unique phospholipid composition, a feature essential for normal cilia formation and function. Recent studies have illustrated that distinct phosphoinositide lipid species localise to specific cilia subdomains, and have begun to build a ‘phosphoinositide map’ of the cilium. The abundance and localisation of phosphoinositides are tightly regulated by the opposing actions of lipid kinases and lipid phosphatases that have also been recently discovered at cilia. The critical role of phosphoinositides in cilia biology is highlighted by the devastating consequences of genetic defects in cilia-associated phosphoinositide regulatory enzymes leading to ciliopathy phenotypes in humans and experimental mouse and zebrafish models. Here we provide a general introduction to primary cilia and the roles phosphoinositides play in cilia biology. In addition to increasing our understanding of fundamental cilia biology, this rapidly expanding field may inform novel approaches to treat ciliopathy syndromes caused by deregulated phosphoinositide metabolism.

Review on Infectious Diseases in India and their respective diagnostic platforms.

2021 ◽  
Vol 9 (11) ◽  
pp. 1862-1871
Author(s):  
PS Chandranand
Keyword(s):  
Infectious Diseases ◽  
Disease Burden ◽  
Respiratory Infections ◽  
Critical Role ◽  
Diagnostic Procedures ◽  
Middle Income Country ◽  
Income Country ◽  
Middle Income ◽  
Lower Middle Income Country ◽  
Illness Prevention

Abstract: India is a lower-middle-income country with improved industrial output and expansion of innovative technologies (information, biopharmaceutical) with some notable health benefits in controlling very few infectious diseases due to an inadequate health system. It mainly focuses on providing medical care for urban population and lacks a common health framework that plays a critical role in illness prevention. However, these diseases are caused not only by a lack of sanitation and population density but also by environmental and behavioural changes. This study reviewed the literature on infectious diseases that cause deaths in India, such as tuberculosis, lower respiratory infections, and Transfusion Transmitted Infections (TTIs), diagnostic procedures for treatment and disease burden. Keywords: lower-middle-income country, Infectious diseases, Transfusion Transmitted Infections (TTIs), disease burden.

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