Suppression of innate immune signaling molecule, MAVS, reduces radiation-induced bystander effect

Abstract

Purpose

Mitochondrial antiviral signaling (MAVS) protein, located in the mitochondrial out-membrane, is necessary for IFN-beta induction and IFN-stimulated gene expression in response to external stress such as viral invasion and ionizing radiation (IR). Although the involvement of radiation induced bystander effect (RIBE) has been investigated for decades for secondary cancer risk related to radiotherapy, the underlying regulatory mechanisms remain largely unclear, especially the roles played by the immune factors such as MAVS.

Material and methods

MAVS gene knockout cells using CRISPR/Cas9 technology were used as donor cells or recipient cells to assess the role of MAVS in RIBE by means of co-cultured system. The micronucleus and γH2AX foci in the recipient cells were counted to demonstrate the degree of RIBE. The reactive oxygen species (ROS) level in the recipient was measured using the fluorescent dye 2′7′-dichlorofluorescein.

Results

Firstly, we found that MAVS expression level was different in A549, BEAS-2B, U937 and HepG2 cells. Cell co-culture experiments showed that MAVS participate in RIBE. Interestingly, the RIBE response was more significant in recipient cells with higher level of MAVS (i.e. A549) than that in recipient cells showing lower level of MAVS (i.e. BEAS-2B). Further, the bystander response was dramatically suppressed in MAVS-silenced A549 and BEAS-2B recipient cells. MAVS-silenced recipient cells exhibited lower level of ROS induced by IR.

Conclusions

Our results indicated that the innate immune signaling molecule MAVS in recipient cells participate in RIBE. ROS is an important factor in RIBE via MAVS pathway and MAVS may be a potential target for the precise radiotherapy and radioprotection.

Keywords:

• MAVS
• irradiation
• ROS
• RIBE

Acknowledgments

The authors sincerely thank Dr. Mei Hong, professor of South China Agricultural University, for her expert revise.

Disclosure statement

The authors do not have any conflicts of interest.

Additional information

Funding

This study was supported by National Natural Science Foundation of China [11705248, U1832101, 11635013] and the Science and Technology Research Project of Gansu Province [NO. 145RTSA012 and 17JR5RA307].

Notes on contributors

Rong Jia

Rong Jia, is a Doctor Student of the Institute of Modern Physics, University of Chinese Academy of Sciences.

Yaxiong Chen

Yaxiong Chen, is an Assistant Researcher of the Institute of Modern Physics, Chinese Academy of Science.

Cong Jia

Cong Jia, is a Postgraduate Student of the College of Life Science, Northwest Normal University.

Burong Hu

Burong Hu, is a Professor of the Department of Radiation Medicine, School of Public Health and Management, Wenzhou Medical University.

Yarong Du

Yarong Du, is an Associate Researcher of the Institute of Modern Physics, Chinese Academy of Sciences.