Extracellular vesicle-mediated regulation of macrophage polarization in bacterial infections

Abstract

Extracellular vesicles (EVs) are nanoscale membrane-enveloped vesicles secreted by prokaryotic and eukaryotic cells, which are commonly defined as membrane vesicles (MVs) and exosomes, respectively. They play critical roles in the bacteria–bacteria and bacteria–host interactions. In infectious diseases caused by bacteria, as the first line of defense against pathogens, the macrophage polarization mode commonly determines the success or failure of the host's response to pathogen aggression. M1-type macrophages secrete pro-inflammatory factors that support microbicidal activity, while alternative M2-type macrophages secrete anti-inflammatory factors that perform an antimicrobial immune response but partially allow pathogens to replicate and survive intracellularly. Membrane vesicles (MVs) released from bacteria as a distinctive secretion system can carry various components, including bacterial effectors, nucleic acids, or lipids to modulate macrophage polarization in host–pathogen interaction. Similar to MVs, bacteria-infected macrophages can secrete exosomes containing a variety of components to manipulate the phenotypic polarization of “bystander” macrophages nearby or long distance to differentiate into type M1 or M2 to regulate the course of inflammation. Exosomes can also repair tissue damage associated with the infection by upregulating the levels of anti-inflammatory factors, downregulating the pro-inflammatory factors, and regulating cellular biological behaviors. The study of the mechanisms by which EVs modulate macrophage polarization has opened new frontiers in delineating the molecular machinery involved in bacterial pathogenesis and challenges in providing new strategies for diagnosis and therapy.

Stratifying macrophages based on their infectious burden identifies novel host targets for intervention during Crohn’s disease associated adherent-invasiveEscherichia coliinfection

“…Interestingly our analyses also indicated that uninfected bystander cells were directly contributing to inflammation despite not being actively infected with AIEC. It is likely that immune activation of these bystander cells is driven by either contact with bacteria, bacteria- derived molecules and vesicles being shed into the media, or immune cell derived TNFα (Bringer et al ., 2012; Jung et al ., 2017; Qu, Zhu and Zhang, 2022). However, the relative contribution of each to bystander cell activation cannot be ascertained from the data generated here, but understanding this could be informative in the context of CD given the importance of TNFα in driving inflammation in CD.…”

Bacterial membrane vesicles in the pathogenesis and treatment of inflammatory bowel disease

“…They contain immunomodulatory molecules that can target host innate immune pattern recognition receptors (PRR) such as Toll-like receptors (TLRs) and Nod-like receptors (NLRs) signaling pathways, thereby stimulating the release of pro-inflammatory cytokines and chemokines, which attract immune cells to the site of inflammation. 114 As a result of the small sizes of MVs and their immunogenicity, their interaction with innate immune cells (macrophages and neutrophils), antigen-presenting cells 115 (dendritic cells), and/or adaptive immune cells (T- and B- cells), leads to the generation of various immune responses as illustrated in Figure 5 . 115 , 116 For instance, the detection of LPS and LOS by TLR-4 results in the activation of nuclear factor-kappa B (NF-κB) and the release of proinflammatory cytokines.…”

Macrophages and stem/progenitor cells interplay in adipose tissue and skeletal muscle: a review

“…Although the exact functions of macrophages will differ depending on location and task at hand, based on their functional program, macrophages are divided into pro-inflammatory [M1, classically activated (AM)], mainly involved in anti-pathogen and anti-tumor responses, and clearing debris, and the anti-inflammatory [M2a-d, alternatively activated (AAM)] macrophages, responsible for tissue repair and regeneration, angiogenesis, and parasite containment ( 29 , 30 , 31 ). M1 are induced by T helper cells type 1 (TH1) cytokines, such as interferon gamma (IFNγ), interleukin (IL)-2, IL-10, and tumor necrosis factor (TNF)-α/β, and produce proinflammatory cytokines, reactive oxygen species (ROS), and inducible nitric oxide synthase (iNOS).…”