CN114908036A - Application of integrin alpha 5 beta 1 receptor in preparation of antibacterial exosomes - Google Patents
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- 108010042918 Integrin alpha5beta1 Proteins 0.000 title claims abstract description 34
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 33
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- 210000002919 epithelial cell Anatomy 0.000 claims abstract description 28
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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Abstract
The invention discloses application of an integrin alpha 5 beta 1 receptor in preparation of an antibacterial exosome, wherein the exosome secreted by the integrin alpha 5 beta 1 receptor on the surface of an epithelial cell when the integrin alpha 5 beta 1 receptor is combined by pathogenic bacteria has an antibacterial effect, so that a host has the effect of combining virulence factors of extracellular pathogens to protect surrounding uninfected cells. The antibacterial exosomes of the integrin α 5 β 1 receptor are: collecting exosomes produced by heat-inactivated GAS stimulating normal epithelial cells and epithelial cells knocked-down for integrin alpha 5 beta 1; the technical scheme disclosed by the invention can enhance the defense capacity of a human body by injecting the artificial exosome into the body to absorb pathogenic bacteria virulence factors or increasing the production of exosomes.
Description
Technical Field
The invention relates to application of integrin alpha 5 beta 1 receptor mediated epithelial cells in forming antibacterial exosomes, and relates to the technical field of immune defense.
Background
In the process of pathogen and host gaming, the sensing ability of host cells to pathogens through surface receptors is a key factor for determining whether host cells can establish effective innate defense first. After the host cell senses the bacteria, the mechanism by which the host cell resists bacterial infection is an important breakthrough for finding new antibacterial components or drug targets.
Early studies found that cell surface receptor integrin α 5 β 1 can induce autophagy that can clear Group A Streptococci (GAS) in epithelial cells; exosomes (Exosomes) research is mostly focused in the field of tumors, but researches on Exosomes and pathogen infection also obtain some instructive results in recent years, but how to determine the composition and functions of Exosomes in the pathogen infection process and how host cells mediate the formation process of infection-related Exosomes is an important problem to be solved by Exosomes in the pathogen-host cell research work.
In our previous experiments, it was also found that exosomes induced by infection of epithelial cells by Group A Streptococcus (GAS) have the ability to bind streptopyretogenic exotoxin (SpeB, an important virulence factor secreted by GAS, capable of degrading host extracellular matrix, immunoglobulin and complement components, destroying host defense system, escaping immune clearance, assisting in GAS diffusion at the initial infection site and invading host deep tissues), so that it cannot bind to epithelial cell membrane to cause destruction, thus greatly reducing the pathogenicity of GAS. We speculate that this antibiotic exosome, termed "decoy", binds to the intracellular free GAS virulence factor SpeB, rendering it inactive, thereby exerting an antibacterial effect and protecting the host cell before the SpeB acts on the cell.
Exosomes closely related to pathogenic microorganism infection may play a role in protecting normal host cells and preventing infection spread when pathogenic microorganisms fail to contact cells. The exosome effectively protects the mouse from being attacked by GAS, and the survival rate of the mouse is improved. And (4) prompting by a result: when infection occurs, host cells secrete an exosome with antibacterial capacity, and a reaction mode that the cells secrete antibacterial substances can be caused by contacting with corresponding receptors on the surface of host cell membranes without pathogenic bacteria invading cells, so that time is taken for establishing rapid defense for the hosts.
It is contemplated that TLR2 and TLR4 are the major pattern recognition receptors for GAS infection, and that TLRs can induce exosome formation upon infection or ligand stimulation. Next, we used siRNA to knock down TLR2 and TLR4 receptors, and found that heat inactivated GAS can also induce a large amount of exosomes to produce and still have antibacterial ability, and the number of intracellular bacteria has no significant difference compared with the no-knock-out TLR2 and TLR4 control group, indicating that TLR2 and TLR4 are not GAS to induce the main receptor of exosomes with antibacterial ability. Integrins are transmembrane receptors that mediate the link between cells and their environment (e.g., extracellular matrix, ECM), and are a major family of cell surface receptors. Most cell surfaces express more than one integrin, which plays a key role in a variety of vital activities. Among them, integrin α 5 β 1 mediates invasion of various intracellular or extracellular bacteria upon infection with pathogenic bacteria. Is integrin α 5 β 1 a key receptor for GAS invasion into epithelial or endothelial cells, and in addition to being a receptor that we have previously discovered to mediate autophagy, also mediates the formation of antibacterial exosomes? At present, no relevant report is found.
Disclosure of Invention
The invention aims to provide application of integrin alpha 5 beta 1 receptor in preparation of antibacterial exosome, wherein the exosome secreted by the integrin alpha 5 beta 1 receptor on the surface of epithelial cells when being combined with pathogenic bacteria components has an antibacterial effect, so that a host has the effect of combining virulence factors of extracellular pathogenic bacteria and protects surrounding uninfected cells.
In order to achieve the technical purpose and achieve the technical effect, the invention is realized by the following technical scheme:
application of integrin alpha 5 beta 1 receptor in preparation of antibacterial exosomes.
Furthermore, the exosome secreted by the epithelial cell surface integrin alpha 5 beta 1 receptor when being bound by pathogenic bacteria components has an antibacterial effect, so that a host has the effect of binding with an extracellular pathogenic bacteria virulence factor and protects surrounding uninfected cells.
Further, the preparation method of the antibacterial exosome of the integrin alpha 5 beta 1 receptor comprises the following steps: harvesting exosomes produced by heat-inactivated GAS stimulating normal epithelial cells and epithelial cells that have been knocked down for integrin α 5 β 1.
It is another object of the present invention to provide an antibacterial exosome obtained by collecting heat-inactivated GAS-stimulated normal epithelial cells and integrin alpha 5 beta 1-knocked-down epithelial cells.
The invention has the beneficial effects that:
the invention aims to provide application of integrin alpha 5 beta 1 receptor in preparation of antibacterial exosome, wherein the exosome secreted by the integrin alpha 5 beta 1 receptor on the surface of epithelial cells when being combined with pathogenic bacteria components has an antibacterial effect, so that a host has the effect of combining virulence factors of extracellular pathogenic bacteria and protects surrounding uninfected cells.
The invention discloses a new mode of integrin alpha 5 beta 1 receptor mediated epithelial cell innate defense; this finding not only increases the knowledge of mammals against infections, but also suggests new strategies for enhancing the immune system, such as enhancing the body's defenses by injecting artificial exosomes into the body to take up pathogenic virulence factors or by increasing exosome production. This mode of action, which is capable of performing innate defense functions at the earliest stages of pathogenic infection, also provides sufficient time for other widely recognized immune defense mechanisms (e.g., pathogenic bacteria activating T cells or producing antibodies), and the host protects against infection through a layered defense function, thereby maintaining a healthy state.
Of course, it is not necessary for any product in which the invention is practiced to achieve all of the above-described advantages at the same time.
Detailed Description
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the present invention will be described in detail with reference to the embodiments.
Example 1
Application of integrin alpha 5 beta 1 receptor in preparation of antibacterial exosomes.
The epithelial cell surface integrin alpha 5 beta 1 receptor has an antibacterial effect on an exosome secreted by the receptor when the receptor is combined by pathogenic bacteria components, so that a host has the effect of combining an extracellular pathogenic bacteria virulence factor and protects surrounding uninfected cells.
Example 2
The preparation method of the antibacterial exosome of the integrin alpha 5 beta 1 receptor comprises the following steps:
harvesting exosomes produced by heat-inactivated GAS stimulating normal epithelial cells and epithelial cells that have been knocked down for integrin α 5 β 1.
Example 3
An antibacterial exosome obtained by collecting heat-inactivated GAS-stimulated normal epithelial cells and integrin alpha 5 beta 1-knocked-down epithelial cells.
The invention aims to provide application of integrin alpha 5 beta 1 receptor in preparation of antibacterial exosome, wherein the exosome secreted by the integrin alpha 5 beta 1 receptor on the surface of epithelial cells when being combined with pathogenic bacteria components has an antibacterial effect, so that a host has the effect of combining virulence factors of extracellular pathogenic bacteria and protects surrounding uninfected cells.
The invention discloses a new mode of integrin alpha 5 beta 1 receptor mediated epithelial cell innate defense; this finding not only increases the knowledge of mammals against infections, but also suggests new strategies for enhancing the immune system, such as enhancing the body's defenses by injecting artificial exosomes into the body to take up pathogenic virulence factors or by increasing exosome production. This mode of action, which is capable of performing innate defense functions at the earliest stages of pathogenic infection, also provides sufficient time for other widely recognized immune defense mechanisms (e.g., pathogenic bacteria activating T cells or producing antibodies), and the host protects against infection through a layered defense function, thereby maintaining a healthy state.
In the description herein, references to the description of "one embodiment," "an example," "a specific example" or the like are intended to mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
The preferred embodiments of the invention disclosed above are intended to be illustrative only. The preferred embodiments are not intended to be exhaustive or to limit the invention to the precise embodiments disclosed. Obviously, many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described in order to best explain the principles of the invention and the practical application, to thereby enable others skilled in the art to best utilize the invention. The invention is limited only by the claims and their full scope and equivalents.
Claims (4)
1. Application of integrin alpha 5 beta 1 receptor in preparation of antibacterial exosomes.
2. Use of the integrin α 5 β 1 receptor of claim 1 for the preparation of antibacterial exosomes, wherein: the epithelial cell surface integrin alpha 5 beta 1 receptor has an antibacterial effect on an exosome secreted by the receptor when the receptor is combined by pathogenic bacteria components, so that a host has the effect of combining an extracellular pathogenic bacteria virulence factor and protects surrounding uninfected cells.
3. Use of the integrin α 5 β 1 receptor of claim 2 for the preparation of antibacterial exosomes, wherein: the preparation method of the antibacterial exosome of the integrin alpha 5 beta 1 receptor comprises the following steps: harvesting exosomes produced by heat-inactivated GAS stimulating normal epithelial cells and epithelial cells that have been knocked down for integrin α 5 β 1.
4. An antibacterial exosome, characterized by: stimulating normal epithelial cells by collecting heat-inactivated GAS and knocking down integrin alpha 5 beta 1 epithelial cells.
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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CN109666695A (en) * | 2018-12-26 | 2019-04-23 | 上海交通大学医学院附属第九人民医院 | A kind of excretion body carrier and its preparation method and application of targeted integration element α v β 3 |
CN110613728A (en) * | 2017-12-11 | 2019-12-27 | 浙江大学 | Application of NK cell exosome hsa-miR-9773 in antibiosis |
KR20210049014A (en) * | 2019-10-24 | 2021-05-04 | 가톨릭대학교 산학협력단 | COMPOSITION INCLUDING EXOSOME CONTAINING INTEGRIN α6 AND αX FOR PREVENTING OR TREATING GASTRIC CANCER |
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- 2022-05-07 CN CN202210492186.1A patent/CN114908036A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110613728A (en) * | 2017-12-11 | 2019-12-27 | 浙江大学 | Application of NK cell exosome hsa-miR-9773 in antibiosis |
CN109666695A (en) * | 2018-12-26 | 2019-04-23 | 上海交通大学医学院附属第九人民医院 | A kind of excretion body carrier and its preparation method and application of targeted integration element α v β 3 |
KR20210049014A (en) * | 2019-10-24 | 2021-05-04 | 가톨릭대학교 산학협력단 | COMPOSITION INCLUDING EXOSOME CONTAINING INTEGRIN α6 AND αX FOR PREVENTING OR TREATING GASTRIC CANCER |
Non-Patent Citations (3)
Title |
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JIACHAO WANG等: "Integrin α5β1, as a Receptor of Fibronectin, Binds the FbaA Protein of Group A Streptococcus To Initiate Autophagy during Infection", 《MBIO .》, vol. 11, no. 3, pages 00771 - 20 * |
李凯;郑鹏远;刘志强;陈东晖;: "肠上皮细胞来源的整合素αVβ6对肠道树突状细胞TGF-β1表达的影响", 世界华人消化杂志, no. 17, pages 1642 - 1648 * |
王家超等: "整合素α5β1受体介导具有抗菌作用外泌体产生的机制研究", 《第十四届全国免疫学学术大会论文摘要汇编 中国免疫学会》, pages 192 * |
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