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International journal of molecular sciences2022; 23(17); 9742; doi: 10.3390/ijms23179742

Rhodococcus equi-Derived Extracellular Vesicles Promoting Inflammatory Response in Macrophage through TLR2-NF-κB/MAPK Pathways.

Xu, Z
·
Hao, X
·
Li, M
·
Luo, H

Abstract: Rhodococcus equi (R. equi) is a Gram-positive coccobacillus that causes pneumonia in foals of less than 3 months, which have the ability of replication in macrophages. The ability of R. equi persist in macrophages is dependent on the virulence plasmid pVAPA. Gram-positive extracellular vesicles (EVs) carry a variety of virulence factors and play an important role in pathogenic infection. There are few studies on R. equi-derived EVs (R. equi-EVs), and little knowledge regarding the mechanisms of how R. equi-EVs communicate with the host cell. In this study, we examine the properties of EVs produced by the virulence strain R. equi 103+ (103+-EVs) and avirulenct strain R. equi 103− (103−-EVs). We observed that 103+-EVs and 103−-EVs are similar to other Gram-positive extracellular vesicles, which range from 40 to 260 nm in diameter. The 103+-EVs or 103−-EVs could be taken up by mouse macrophage J774A.1 and cause macrophage cytotoxicity. Incubation of 103+-EVs or 103−-EVs with J774A.1 cells would result in increased expression levels of IL-1β, IL-6, and TNF-α. Moreover, the expression of TLR2, p-NF-κB, p-p38, and p-ERK were significantly increased in J774A.1 cells stimulated with R. equi-EVs. In addition, we presented that the level of inflammatory factors and expression of TLR2, p-NF-κB, p-p38, and p-ERK in J774A.1 cells showed a significant decreased when incubation with proteinase K pretreated-R. equi-EVs. Overall, our data indicate that R. equi-derived EVs are capable of mediating inflammatory responses in macrophages via TLR2-NF-κB/MAPK pathways, and R. equi-EVs proteins were responsible for TLR2-NF-κB/MAPK mediated inflammatory responses in macrophage. Our study is the first to reveal potential roles for R. equi-EVs in immune response in R. equi-host interactions and to compare the differences in macrophage inflammatory responses mediated by EVs derived from virulent strain R. equi and avirulent strain R. equi. The results of this study have improved our knowledge of the pathogenicity of R. equi.

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Publication Date: 2022-08-28 PubMed ID: 36077142PubMed Central: PMC9456034DOI: 10.3390/ijms23179742Google Scholar: Lookup

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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study investigates the effects of extracellular vesicles from a bacterium called Rhodococcus equi on inflammatory responses in macrophages, and finds that these vesicles can mediate inflammation through specific cellular signaling pathways. It offers new insights into the bacterium’s pathogenicity and potential interaction with its host.

Understanding the Studied Microorganism

Rhodococcus equi is a kind of bacterium capable of causing pneumonia in very young foals (baby horses). This bacteria can reproduce inside certain immune cells called macrophages.
The ability of R. equi to survive within macrophages is based on a particular virulence factor found on a plasmid, a standalone piece of DNA, known as pVAPA.

The Importance of Extracellular Vesicles (EVs)

Extracellular vesicles are small particles produced by cells which can carry a variety of substances, such as proteins and genetic material.
In the context of bacterial infections, extracellular vesicles can contain virulence factors and are known to play significant roles in pathogenesis.
The researchers in this study focused specifically on extracellular vesicles produced by R. equi, which have previously been understudied, aiming to clarify their impact on host cells.

Key Experimental Observations

The researchers found that the extracellular vesicles from two different strains of R. equi, one virulent and one avirulent, were similar in properties to those of other Gram-positive bacteria and could be taken up by macrophages.
Exposure to these vesicles led to increased expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and other key proteins which are participants in inflammatory signaling pathways (TLR2, p-NF-κB, p-p38, and p-ERK) in the macrophages.
Treatment of the vesicles with proteinase K, an enzyme that degrades proteins, significantly diminished these inflammatory responses, suggesting that proteins within the vesicles were responsible for the observed effects.

Conclusion and Implications

The data suggests that extracellular vesicles produced by R. equi can stimulate inflammation in macrophages through specific cellular signaling pathways (TLR2-NF-κB/MAPK).
The study provides valuable insights into the pathogenicity of R. equi, its interaction with the host immune system, and potential therapeutic targets for intervention. This could also pave way for future research into bacterial extracellular vesicles and their roles in host-pathogen interactions.

Cite This Article

APA

Xu Z, Hao X, Li M, Luo H. (2022). Rhodococcus equi-Derived Extracellular Vesicles Promoting Inflammatory Response in Macrophage through TLR2-NF-κB/MAPK Pathways. Int J Mol Sci, 23(17), 9742. https://doi.org/10.3390/ijms23179742

Publication

International journal of molecular sciences

ISSN: 1422-0067

NlmUniqueID: 101092791

Country: Switzerland

Language: English

Volume: 23

Issue: 17

PII: 9742

Researcher Affiliations

Xu, Zhaokun

Life Science School, Ningxia University, Yinchuan 750021, China.
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Ningxia University, Yinchuan 750021, China.

Hao, Xiujing

Life Science School, Ningxia University, Yinchuan 750021, China.
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Ningxia University, Yinchuan 750021, China.

Li, Min

Life Science School, Ningxia University, Yinchuan 750021, China.
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Ningxia University, Yinchuan 750021, China.

Luo, Haixia

Life Science School, Ningxia University, Yinchuan 750021, China.
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Ningxia University, Yinchuan 750021, China.

MeSH Terms

Actinomycetales Infections / metabolism
Actinomycetales Infections / veterinary
Animals
Extracellular Vesicles / metabolism
Horses
Macrophages / metabolism
Mice
NF-kappa B / metabolism
Rhodococcus equi / genetics
Toll-Like Receptor 2 / genetics
Toll-Like Receptor 2 / metabolism

Grant Funding

31960694 / National Natural Science Foundation of China
31760035 / National Natural Science Foundation of China
2021AAC05008 / Excellent Youth Project of Ningxia Natural Science Foundation
no / Ningxia Overseas Students Innovation and Entrepreneurship Project

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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