Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity

Wu, Meng Hsing; Jia, Beibei; Li, Mo-fei

doi:10.3389/fimmu.2022.813173

Cited by 15 publications

(14 citation statements)

References 83 publications

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“…During implantation of foreign medical devices, the complement system is easily activated, which subsequently leads to immune cytolysis and hemolysis . Based on the results of the ELISA kit and the analysis of variance (Figure A), there was no significant difference between GSAs and the blank control and no activation of C3a.…”

Section: Resultsmentioning

confidence: 99%

Artificial Extracellular Matrix Composed of Heparin-Mimicking Polymers for Efficient Anticoagulation and Promotion of Endothelial Cell Proliferation

Wang

Wang²,

Feng

et al. 2022

ACS Appl. Mater. Interfaces

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Heparin-mimicking polymers have emerged as an alternative to heparin to construct effective and safe anticoagulant surfaces. However, the present heparin-mimicking polymers are usually limited to the combinations of glucose and sulfonic acid units, and the structure origin of their anticoagulant properties remains vague. Inspired by the structure of natural heparin, we synthesized a series of novel heparin-mimicking polymers (named GSAs) composed of three units, glucose, sulfonic acid, and carboxylic acid. Then, we constructed artificial extracellular matrices composed of GSAs and two typical cationic polymers, polyethyleneimine and chitosan, to investigate the anticoagulation and endothelialization of GSAs. By changing the ratio of the three units, their functions in the matrices were studied systematically. We found that an increase in the sulfonic acid content enhanced surface anticoagulant activity, an increase in glucose and sulfonic acid content promoted the proliferation of human umbilical vein vascular endothelial cells, and an increase in the carboxylic acid content inhibited the adherence of human umbilical vein vascular smooth muscle cells. This work uncovers the important role of the GSAs structure to the anticoagulation properties, which sheds new light on the design and preparation of heparin-mimicking polymers for practical engineering applications.

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Section: Resultsmentioning

confidence: 99%

Artificial Extracellular Matrix Composed of Heparin-Mimicking Polymers for Efficient Anticoagulation and Promotion of Endothelial Cell Proliferation

Wang

Wang²,

Feng

et al. 2022

ACS Appl. Mater. Interfaces

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“…Complement is activated in macrophages invaded by T. gondii . The central step of complement activation is the conversion of C3 to C3a, which is responsible for clearing pathogens ( Wu et al, 2022 ). Does the local activation of C3 regulate macrophage xenophagy through these intermediate products?…”

Section: Resultsmentioning

confidence: 99%

Locally generated C3 regulates the clearance of Toxoplasma gondii by IFN-γ-primed macrophage through regulation of xenophagy

et al. 2022

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Exogenous pathogen infection can induce autophagy in cells. Autophagy is essential for cell survival, development, and homeostasis. It not only regulates cell defense and stress, but also has a close relationship with innate and adaptive immunity. Complement is an important part of innate immunity, which could be activated by three approaches, including classic, alternative, and lectin pathways. All the three pathways result in the activation of C3, and generate anaphylatoxin fragments C3a and C5a, and formation of the membrane attack complex. Either C3a or C5a induces the inflammatory cytokines through binding to C3aR or C5aR, respectively. However, it is still unknown whether the complement could regulate the autophagy of intracellular microorganisms or not. In this study, we constructed a Toxoplasma gondii (T. gondii) and macrophages co-culture experimental model using T. gondii expressing enhanced green fluorescence protein (EGFP) fluorescence and C3−/-C57BL/6 J mice for that T. gondii invaded peritoneal macrophages in mice. Western blot, laser confocal microscopy (LCM), and transmission electron microscopy (TEM) were used to observe the changes of autophagy between the macrophages from wild-type (WT) and C3−/− mice. Flow cytometry and LCM were used to investigate the effect of autophagy on the killing ability of macrophages against T. gondii. Here, we found that local C3 could suppress not only the canonical autophagy of macrophage, but also the xenophagy to T. gondii. Interestingly, the inhibition of C3 on host cell autophagy could significantly suppress the clearance of T. gondii by the IFN-γ-primed macrophage. Finally, we investigated the mechanism of the autophagy regulation of C3 that the effect of C3 on the macrophage-specific autophagy against T. gondii depends on mTOR. And, there is C3a but not C5a/C5aR involved in regulating macrophage xenophagy against T. gondii. Collectively, our findings suggest locally generated C3 regulates the clearance of T. gondii by Macrophage through the regulation of the non-canonical IFN-γ-dependent autophagy pathway, and paint a clearer picture in the regulation of autophagy by innate immune components.

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“…Thus, the deficiency of C3 leads to severe a bacterial infection, including those caused by meningococci and pneumococci ( 37 ). The exogenous administration of complement component C3 and the active form C3a in Japanese flounder increased its survival against bacterial infection by inducing chemotaxis to peripheral blood leukocytes ( 38 ). Given the importance of C3 and C5b-9, enhancing C3 and C5-9 deposition is key to boost the complement killing activity.…”

Section: Discussionmentioning

confidence: 99%

Functional proteomics identify mannitol metabolism in serum resistance and therapeutic implications in Vibrio alginolyticus

Kou

Chen

et al. 2022

Front. Immunol.

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Serum resistance is recognized as one of the most important pathogenic traits of bacterial pathogens, and no control measure is available. Based on our previous discovery that pathogenic Escherichia coli represses glycine, serine, and threonine metabolism to confer serum resistance and that the reactivation of this pathway by exogenous glycine could restore serum sensitivity, we further investigate the mechanism underlying the action of glycine in Vibrio alginolyticus. Thus, V. alginolyticus is treated with glycine, and the proteomic change is profiled with tandem mass tag-based quantitative proteomics. Compared to the control group, glycine treatment influences the expression of a total of 291 proteins. Among them, a trap-type mannitol/chloroaromatic compound transport system with periplasmic component, encoded by N646_0992, is the most significantly increased protein. In combination with the pathway enrichment analysis showing the altered fructose and mannitol metabolism, mannitol has emerged as a possible metabolite in enhancing the serum killing activity. To demonstrate this, exogenous mannitol reduces bacterial viability. This synergistic effect is further confirmed in a V. alginolyticus–Danio rerio infection model. Furthermore, the mechanism underlying mannitol-enabled serum killing is dependent on glycolysis and the pyruvate cycle that increases the deposition of complement components C3b and C5b-9 on the bacterial surface, whereas inhibiting glycolysis or the pyruvate cycle significantly weakened the synergistic effects and complement deposition. These data together suggest that mannitol is a potent metabolite in reversing the serum resistance of V. alginolyticus and has promising use in aquaculture.

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Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity

Cited by 15 publications

References 83 publications

Artificial Extracellular Matrix Composed of Heparin-Mimicking Polymers for Efficient Anticoagulation and Promotion of Endothelial Cell Proliferation

Artificial Extracellular Matrix Composed of Heparin-Mimicking Polymers for Efficient Anticoagulation and Promotion of Endothelial Cell Proliferation

Locally generated C3 regulates the clearance of Toxoplasma gondii by IFN-γ-primed macrophage through regulation of xenophagy

Functional proteomics identify mannitol metabolism in serum resistance and therapeutic implications in Vibrio alginolyticus

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