Significance of extracellular vesicles in orchestration of immune responses in Mycobacterium tuberculosis infection

Mycobacterium tuberculosis (M.tb), the causative agent of Tuberculosis, is an intracellular bacterium well known for its ability to subvert host energy and metabolic pathways to maintain its intracellular survival. For this purpose, the bacteria utilize various mechanisms of which extracellular vehicles (EVs) related mechanisms attracted more attention. EVs are nanosized particles that are released by almost all cell types containing active biomolecules from the cell of origin and can target bioactive pathways in the recipient cells upon uptake. It is hypothesized that M.tb dictates the processes of host EV biogenesis pathways, selectively incorporating its molecules into the host EV to direct immune responses in its favor. During infection with Mtb, both mycobacteria and host cells release EVs. The composition of these EVs varies over time, influenced by the physiological and nutritional state of the host environment. Additionally, different EV populations contribute differently to the pathogenesis of disease at various stages of illness participating in a complex interplay between host cells and pathogens. These interactions ultimately influence immune responses and disease outcomes. However, the precise mechanisms and roles of EVs in pathogenicity and disease outcomes remain to be fully elucidated. In this review, we explored the properties and function of EVs in the context of M.tb infection within the host microenvironment and discussed their capacity as a novel therapeutic strategy to combat tuberculosis

Crosstalk between mast cells and adipocytes in physiologic and pathologic conditions

Excessive fatty acids and glucose uptake support the infiltration of adipose tissue (AT) by a variety of immune cells including neutrophils, pro-inflammatory M1 macrophages, and mast cells (MCs). These cells promote inflammation by releasing pro-inflammatory mediators. The involvement of MCs in AT biology is supported by their accumulation in the AT of obese individuals along with significantly higher serum levels of MC-derived tryptase. AT-resident MCs under the influence of locally derived adipokines such as leptin become activated and release pro-inflammatory cytokines including TNFα that worsens the inflammatory state. MCs support angiogenesis in AT by releasing chymase and inducing preadipocyte differentiation and also the proliferation of adipocytes through 15-deoxy-delta PGJ2/PPARγ interaction. Additionally, they contribute to the remodeling of the AT extracellular matrix (ECM) and play a role in the recruitment and activation of leukocytes. MC degranulation has been linked to brown adipocyte activation, and evidence indicates an important link between MCs and the appearance of BRITE/beige adipocytes in white AT. Cell crosstalk between MCs and AT-resident cells, mainly adipocytes and immune cells, shows that these cells play a critical role in the regulation of AT homeostasis and inflammation

Cellular and molecular mechanisms of mast cells in atherosclerotic plaque progression and destabilization

Mast cells (MCs) are commonly recognized for their crucial involvement in the pathogenesis of allergic diseases, but over time, it has come to light that they also play a role in the pathophysiology of non-allergic disorders including atherosclerosis. The involvement of MCs in the pathology of atherosclerosis is supported by their accumulation in atherosclerotic plaques upon their progression and the association of intraplaque MC numbers with acute cardiovascular events. MCs that accumulate within the atherosclerotic plaque release a cocktail of mediators through which they contribute to neovascularization, plaque progression, instability, erosion, rupture, and thrombosis. At a molecular level, MC-released proteases, especially cathepsin G, degrade low-density lipoproteins (LDL) and mediate LDL fusion and binding of LDL to proteoglycans (PGs). Through a complicated network of chemokines including CXCL1, MCs promote the recruitment of among others CXCR2+ neutrophils, therefore, aggravating the inflammation of the plaque environment. Additionally, MCs produce extracellular traps which worsen inflammation and contribute to atherothrombosis. Altogether, evidence suggests that MCs actively, via several underlying mechanisms, contribute to atherosclerotic plaque destabilization and acute cardiovascular syndromes, thus, making the study of interventions to modulate MC activation an interesting target for cardiovascular medicine.Biopharmaceutic

Perivascular macrophages in health and disease

Macrophages are a heterogeneous group of cells that are capable of carrying out distinct functions in different tissues, as well as in different locations within a given tissue. Some of these tissue macrophages lie on, or close to, the outer (abluminal) surface of blood vessels and perform several crucial activities at this interface between the tissue and the blood. In steady-state tissues, these perivascular macrophages maintain tight junctions between endothelial cells and limit vessel permeability, phagocytose potential pathogens before they enter tissues from the blood and restrict inappropriate inflammation. They also have a multifaceted role in diseases such as cancer, Alzheimer disease, multiple sclerosis and type 1 diabetes. Here, we examine the important functions of perivascular macrophages in various adult tissues and describe how these functions are perturbed in a broad array of pathological conditions

Mast cell-mediated mechanistic pathways in organ transplantation

Adaptive immunity has gained importance in transplant immunology for years, based on models in which T-cells orchestrate the immune responses during rejection. Most recently, researches revealed that innate immune cells, including mast cells (MCs) also play a pivotal role in allograft rejection. MC mediated immunoregulatory responses influence the innate and adaptive immune responses. Their capability to produce an array of both pro-inflammatory and anti-inflammatory mediators, expressing a wide range of costimulatory molecules in addition to acting as antigen-presenting cells (APCs), make them effective immune cells far beyond their classical role as primary orchestrator cells of allergy. Activated regulatory Tcells (Treg) cells contribute to MC recruitment into grafts by releasing interleukin (IL)-9. Tregs are capable of stabilizing MCs and suppressing IgE mediated degranulation through interaction of Treg expressing OX40 with MCs expressing OX40L. MCs in turn release transforming growth factor (TGF)-β and IL-10 which possess suppressive properties. Thus, these cells can suppress the proliferation of T-cells and support the generation of Tregs. MCs in addition to orchestrating immune responses in grafts by cell-to-cell interactions with variety of immune cells, cause histologic changes, mainly fibrosis by releasing mediators such as histamine, fibroblast growth factor-2 (FGF-2), TGF-β, chymase, and cathepsin G. The role of MCs in transplant rejection remains controversial. The accumulation of MCs in rejected grafts suggests that they play a role in preventing graft tolerance, and contribute to the progression of chronic rejection of allografts. However, high expression of MC-related gene products in tolerant grafts and their known interaction with Tregs on the other hand, support the notion that they are an integral component in achieving peripheral tolerance

Biodegradable Materials for Sustainable Health Monitoring Devices

The recent advent of biodegradable materials has offered huge opportunity to transform healthcare technologies by enabling sensors that degrade naturally after use. The implantable electronic systems made from such materials eliminate the need for extraction or reoperation, minimize chronic inflammatory responses, and hence offer attractive propositions for future biomedical technology. The eco-friendly sensor systems developed from degradable materials could also help mitigate some of the major environmental issues by reducing the volume of electronic or medical waste produced and, in turn, the carbon footprint. With this background, herein we present a comprehensive overview of the structural and functional biodegradable materials that have been used for various biodegradable or bioresorbable electronic devices. The discussion focuses on the dissolution rates and degradation mechanisms of materials such as natural and synthetic polymers, organic or inorganic semiconductors, and hydrolyzable metals. The recent trend and examples of biodegradable or bioresorbable materials-based sensors for body monitoring, diagnostic, and medical therapeutic applications are also presented. Lastly, key technological challenges are discussed for clinical application of biodegradable sensors, particularly for implantable devices with wireless data and power transfer. Promising perspectives for the advancement of future generation of biodegradable sensor systems are also presented