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Research
ToxoGRA15II promote macrophages polarization against Hepatic carcinoma by targeting TRAF6
Yihong Cai
Anhui Medical University
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
Background: There is increasing evidence that tumor-associated macrophages play an important role in the development of tumors. The more macrophages, the faster the tumors develop. On the one hand, studies have shown that the dense granule protein molecule of Toxoplasma gondii (ToxoGRA15II) tends to induce the differentiation of classically activated macrophages (M1). GRA15II can also induce M2 reversal polarized to M1. Promote the occurrence of Th1 immune response.
Methods: Here, we constructed LV-gra15Ⅱ, which was transferred to M1-like and/or M2-like macrophages. Furthermore, we injected LV-gra15Ⅱ by vein into tumor bearing C57BL/6 mice.
Results: We found that M2-like macrophages could be polarized to M1-like macrophages, inducing NO, IL12, TNF-αexpression. Mechanistically, ToxoGRA15Ⅱ activate NF-κB signaling pathway by binding to TRAF6. Additionally, LV-gra15Ⅱ promoted p65 nuclear translocation to polarize TAM to M1-like macrophages and induce IFN-γ,TNF-α,IL12, NO expression, inhibiting tumor growth. Subsequently, ToxoGRA15Ⅱ has a role in cancer pathway and metabolism.
Conclusions: Taken together, these findings could lead to the development of immunotherapy strategies to tumor, due to ToxoGRA15Ⅱ as polypeptide effector molecule of T.gondii and non-toxicity to mammalians.
Keywords
Toxoplasma gondii, dense granule protein GRA15, hepatocellular carcinoma, macropahges, polarization, TRAF6, NF-κB
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This is a preprint. It has not completed peer review.
Research
ToxoGRA15II promote macrophages polarization against Hepatic carcinoma by targeting TRAF6
Yihong Cai
Anhui Medical University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 18 Dec, 2019
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Parasitology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: There is increasing evidence that tumor-associated macrophages play an important role in the development of tumors. The more macrophages, the faster the tumors develop. On the one hand, studies have shown that the dense granule protein molecule of Toxoplasma gondii (ToxoGRA15II) tends to induce the differentiation of classically activated macrophages (M1). GRA15II can also induce M2 reversal polarized to M1. Promote the occurrence of Th1 immune response.
Methods: Here, we constructed LV-gra15Ⅱ, which was transferred to M1-like and/or M2-like macrophages. Furthermore, we injected LV-gra15Ⅱ by vein into tumor bearing C57BL/6 mice.
Results: We found that M2-like macrophages could be polarized to M1-like macrophages, inducing NO, IL12, TNF-αexpression. Mechanistically, ToxoGRA15Ⅱ activate NF-κB signaling pathway by binding to TRAF6. Additionally, LV-gra15Ⅱ promoted p65 nuclear translocation to polarize TAM to M1-like macrophages and induce IFN-γ,TNF-α,IL12, NO expression, inhibiting tumor growth. Subsequently, ToxoGRA15Ⅱ has a role in cancer pathway and metabolism.
Conclusions: Taken together, these findings could lead to the development of immunotherapy strategies to tumor, due to ToxoGRA15Ⅱ as polypeptide effector molecule of T.gondii and non-toxicity to mammalians.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5