Microbe-host interactions: structure and functions of Gram-negative bacterial membrane vesicles

Abstract

Bacteria-host interaction is a common, relevant, and intriguing biological phenomena. The host reacts actively or passively to the bacteria themselves, their products, debris, and so on, through various defense systems containing the immune system, the bacteria communicate with the local or distal tissues of the host via their own surface antigens, secreted products, nucleic acids, etc., resulting in relationships of attack and defense, adaptation, symbiosis, and even collaboration. The significance of bacterial membrane vesicles (MVs) as a powerful vehicle for the crosstalk mechanism between the two is growing. In the recent decade, the emergence of MVs in microbial interactions and a variety of bacterial infections, with multiple adhesions to host tissues, cell invasion and evasion of host defense mechanisms, have brought MVs to the forefront of bacterial pathogenesis research. Whereas MVs are a complex combination of molecules not yet fully understood, research into its effects, targeting and pathogenic components will advance its understanding and utilization. This review will summarize structural, extraction and penetration information on several classes of MVs and emphasize the role of MVs in transport and immune response activation. Finally, the potential of MVs as a therapeutic method will be highlighted, as will future research prospects.

Keywords: Gram-negative; application; immune response; interactions; membrane vesicles.

Figure 1

MVs formation and influence factors. (A) β-lactamase affects cell wall biosynthesis and ciprofloxacin causes DNA damage. (B) Biosynthetic imbalance, misfolded proteins buildup, leading to outer membrane protrusion. (C) Outer membrane stress is caused by abnormal iron-restricted phosphate transport, gentamicin and mucin. (D) Induction of SOS response by DNA damaging agents, UV rays, ciprofloxacin and other external circumstances resulting in “bubbling cell death.” (E) Insertion of hydrophobic molecules such as PQS and toluene, leading to altered outer membrane curvature. BioRender.com was used to create this.

Figure 2

MVs entering into and interacting with cells. (A) Various ways for MVs entry into the recipient cells. Route 1, represent macropinocytosis pathway; route 2, represent clathrin-protein-mediated endocytosis pathway; route 3, represent caveolae-mediated endocytosis pathway; route 4, represent lipid raft-mediated endocytosis pathway; route 5, represent direct membrane fusion pathway. (B) The toxins released by MVs target particular sites within the host cell. (C) NF-κB promotes extracellular production of human beta defensins (HBDs) and increased NOD1-dependent production of CCL2, CCL20, CXCL1, CXCL2, CXCL8 and IL-6, as well as upregulation of CD80, CD83 and HLA-DR, which triggers TH2 and TH17 cellular responses to generate IL-4, IL-13 and IL-17. BioRender.com was used to create this.

Figure 3

MVs in immunomodulation. (A) CD80, CD86, HLA-DR, ICAM1, CCLD2, CCL3, CCL5, CXCL8, IL-1β, IL-6, IL-10, IL-12p40, IL-12p70 and TNF expression were increased, and CD14 expression and lipopolysaccharide-mediated responses were decreased. (B) CCL2, IFNγ, IL-12p40, IL-12p70, IL-16, and TNF levels were elevated, while phagocytic and chemotactic activities were reduced. (C) CCL3, CCL4, CXCL8, IL-1β, NETs and TNF were elevated, phagocytic and chemotactic activities were decreased. BioRender.com was used to create this.

Figure 4

MVs in clinical applications. (A) Vaccine-associated proteins are encapsulated during vesicle formation, and the complex is administered into tumor-bearing animals, resulting in a decrease in tumor cells and an increase in CTL cells via immunomodulation or direct interaction with tumor tissue. (B) Tumor cell membranes and bacterial vesicles are combined to generate new vesicles, which are then used as adjuvants in customized immunotherapy, inguinal lymph node activation, lung metastasis inhibition, and recurrence inhibition. (C) The medication penetrates during vesicle formation and afterwards targets the target cells, increasing cell sensitivity and encouraging target cell attack and cell destruction by immune cells. BioRender.com was used to create this.