The human body is a “superorganism” that harbors trillions of microbes, most of which colonize the gastrointestinal (GI) tract. The gut microbiome and mammalian host interact with each other and form a mutual relationship, which plays important roles in physiology and immunity. While intestinal epithelium forms the first line of barrier interacting with the commensal microbiota, diverse immune cells, stromal cells and nerve cells distribute in the lamina propria, forming a complex network regulating each other under physiological and pathological conditions.

The molecular base for the dialog between microbiome and host immune system is largely through pattern recognition receptors (PRRs), which are mainly expressed by innate immune cells. PRR-mediated signaling is critical to understand microbiome’s impact on immune response locally and systemically. Upon sensing of microbes associated molecular patterns (MAMPs), PRRs initiate signaling cascades leading to inflammatory responses. Although controlled inflammatory response is considered beneficial, inflammation can be rather detrimental if dysregulated. Diseases such as bacterial and viral infections, cancer, auto-immune diseases and metabolic disorders all involve uncontrolled inflammation in respective tissues.

Upon challenge by pathogens or sterile stimuli, a group of PRRs including NLRP3 and AIM2 can recruit ASC and pro-caspase-1 to assemble an inflammasome. The assembly of inflammasome leads to caspase-1 activation, which cleaves pro-IL-1β and pro-IL-18 to form mature IL-1β and IL-18 for secretion. Caspase-1 also cleaves GSDMD and results in pyroptosis. Inflammasome activation also leads to unconventional protein secretion.

Our lab aims to elucidate the intricate interplay between the innate immune system and the microbiome in the context of various diseases, mainly from the angle of inflammasome and PRR signaling in multiple types of host cells in the gut and lung.

The primary objectives of this unit are:

1. To investigate the impact of the microbiome on the host's innate immune response during viral infections and cancer, particularly in mucosal organs such as the lung and gut.

2. To elucidate the mechanistic pathways through which the innate immune system, especially the inflammasome, affects the microbiome under physiological and pathological conditions. 

3. To identify key microbial components that modulate innate immunity, thus exploring potential intervention strategies to improve disease management.

Selected publications

2023：

1. Yuhui Gao^#, Shi Yu^#, Mengdan Chen, Xun Wang, Lei Pan, Bin Wei, Guangxun Meng^*.cFLIPS regulates alternative NLRP3 inflammasome activation in human monocytes. Cell Mol Immunol. 2023 Oct;20(10):1203-1215. doi: 10.1038/s41423-023-01077-y. PMID: 37591930.

2. Mengdan Chen^#, Shi Yu^#, Yuhui Gao, Jiaxun Li, Xun Wang , Bin Wei,Guangxun Meng^* , TRAF6-TAK1-IKKβ pathway mediates TLR2 agonists activating “one-step”NLRP3 inflammasome in human monocytes.Cytokine 169.(2023) 156302. doi: 10.1016/j.cyto.2023.156302. Epub 2023 Jul 20. PMID: 37480791.

3. Junling Niu, Guangxun Meng^*, Roles and Mechanisms of NLRP3 in Influenza Viral Infection.Viruses. 2023 Jun 8;15(6):1339. doi: 10.3390/v15061339. PMID: 37376638.

4. Junling Niu, Mengmeng Cui, Xin Yang, Juan Li, Yuhui Yao, Qiuhong Guo, Ailing Lu, Xiaopeng Qi, Dongming Zhou, Chenhong Zhang,*, Liping Zhao,*, Guangxun Meng,* NLRP3 mediates acetate-enhanced induction of IFN-I to alleviate influenza A virus infection, Nat Commun.. 2023 Feb 6;14(1):642. doi: 10.1038/s41467-023-36323-4. PMID: 36746963.  

2022：

5. Guangxun Meng, Carsten J Kirschning , Rongbin Zhou, Editorial: Patho- and Physiological Roles of Inflammasomes. Front Immunol. 2022 Feb 28;13:857929. doi: 10.3389/fimmu.2022.857929. PMID: 35296078.

6. Shi Yu, Xu Zheng, Bingjie Zhou, Juan Li, Mengdan Chen, Rong Deng, Gary Wong, Dimitri Lavillette*, Guangxun Meng*,       SARS-CoV-2 spike engagement of ACE2 primes S2’ site cleavage and fusion initiation.   Proc Natl Acad Sci U S A. January 4, 2022 119 (1) e2111199119. doi: 10.1073/pnas.2111199119. PMID: 34930824.

2021：

7. 孟广勋，模式识别受体对肠道菌群稳态的影响，中国科学: 生命科学 (2021); doi: 10.1360/SSV-2021-0282

8. Ailing Lu^#; Shuxian Wu^#; Junling Niu; Mengmeng Cui; Mengdan Chen;William L Clap; Betsy J Barnes; Guangxun Meng*; Aim2 Couples with Ube2i for Sumoylation-mediated Repression of Interferon Signatures in Systemic Lupus Erythematosus. Arthritis & Rheumatology. 2021 Aug;73(8):1467-1477. doi: 10.1002/art.41677. Epub 2021 Jul 7. PMID: 33559374.

9. Liqiong Song^#, Yuchun Xiao^#, Xianping Li, Yuanming Huang, Guangxun Meng^*,and Zhihong Ren^*. Activation of the Nlrp3 Inflammasome Contributes to Shiga Toxin-Induced Hemolytic remic Syndrome in a Mouse Model. Front Immunol. 2021 Jan 21;11:619096. doi: 10.3389/fimmu.2020.619096. PMID: 33552083.

2020：

10. Wenjing Li^#, Lei Shi^#, Zhenpeng Zhuang^#, Han Wu^#, Meng Lian, Yihui Chen, Lei Li, Weikai Ge, Qin Jin, Quanjun Zhang, Yu Zhao, Zhaoming Liu, Zhen Ouyang, Yinghua Ye, Yingying Li, Hai Wang, Yuan Liao, Longquan Quan, Lei Xiao, Liangxue Lai^*, Guangxun Meng^* and Kepin Wang^*., Engineered Pigs Carrying a Gain-of-Function NLRP3 Homozygous Mutation Can Survive to Adulthood and Accurately Recapitulate Human Systemic Spontaneous Inflammatory Responses. J Immunol. 2020 Nov 1;205(9):2532-2544. doi: 10.4049/jimmunol.1901468. PMID: 32958688

11. Liqiong Song^# , Xianping Li^# , Yuchun Xiao, Yuanming Huang,  Yongqiang Jiang^*, Guangxun Meng^* and Zhihong Ren^*. Contribution of Nlrp3 Inflammasome Activation Mediated by Suilysin to Streptococcal Toxic Shock-like Syndrome. Frontiers in Microbiology. 2020 Aug 14;11:1788. doi: 10.3389/fmicb.2020.01788. eCollection. PMID: 32922370.

2019：

12. Zheng Li^#, Fujia Yao^#, Guang Xuea ^#, Yongfen Xu, Junling Niu, Mengmeng Cui, Hongbin Wang, Shuxian Wu, Ailing Lu, Jin Zhong, Guangxun Meng^*.Antiviral effects of simeprevir on multiple viruses. Antiviral Research. 2019 Dec;172:104607. doi: 10.1016/j.antiviral.2019.104607. PMID:31563599.  

13. Yihui Chen, Hongbin Wang, Junchen Shen, Rong Deng, Xiaomin Yao, Qiuhong Guo, Ailing Lu1, Bing Sun1, Yan Zhang, Guangxun Meng^*, Gasdermin D Drives the Nonexosomal Secretion of Galectin-3, an Insulin Signal Antagonist, J Immunology. 2019 Nov 15;203(10):2712-2723. doi: 10.4049/jimmunol.1900212. PMID: 31597705.

14. Junling Niu^#, Shuxian Wu^#, Mingkuan Chen, Ke Xu, Qiuhong Guo, Ailing Lu,Liping Zhao, Bing Sun, Guangxun Meng^*. Hyperactivation of the NLRP3 inflammasome protects mice against influenza A virus infection via IL-1β mediated neutrophil recruitment. Cytokine. 2019 Aug;120:115-124. doi: 10.1016/j.cyto.2019.04.019. PMID: 31055218.

15. Zhi Li, Gen Lu, Guangxun Meng^*, Pathogenic fungal infection in the lung. Front Immunol. 2019 Jul 3;10:1524. doi: 10.3389/fimmu.2019.01524. PMID: 31333658.

2018：

16. Hongbin Wang, Zheng Li, Junling Niu, Yongfen Xu, Li Ma, Ailing Lu, XunWang, Zhikang Qian, Zhong Huang,Xia Jin, Qibin Leng, Jianhua Wang, Jin Zhong, Bing Sun and Guangxun Meng^*.Antiviral effects of ferric ammonium citrate. Cell Discovery. 2018, 4 (1) :14. doi: 10.1038/s41421-018-0013-6. PMID: 29619244.

2017：

17. Xiaomin Yao^#, Chenhong Zhang^#, Yue Xing^#, Guang Xue, Qianpeng Zhang, Fengwei Pan, Guojun Wu,Yingxin Hu, Qiuhong Guo, Ailing Lu, Xiaoming Zhang, Rongbin Zhou, Zhigang Tian, Benhua Zeng,Hong Wei, Warren Strober, Liping Zhao^* & Guangxun Meng^*, Remodelling of the gut microbiota by hyperactive NLRP3 induces regulatory T cells to maintain homeostasis, Nature Communications. 2017 Dec 1;8(1):1896. doi: 10.1038/s41467-017-01917-2. PMID: 29196621.

18. Xiang Kong^#, Ai-Ling Lu^#, Xin-Ming Yao, Qiang Hua, Xiao-Yong Li, Li Qin, Hong-Mei Zhang, Guang-Xun Meng^*, and Qing Su^*. Activation of NLRP3 Inflammasome by Advanced Glycation End Products Promotes Pancreatic Islet Damage. Oxid Med Cell Longev (Oxidative Medicine and Cellular Longevity). 2017;2017:9692546. Epub 2017 Nov 5. doi: 10.1155/2017/9692546. PMID: 29230270.

19. Xiaomin Yao and Guangxun Meng^*. Inflammasomes in the Gut Mucosal Homeostasis. Adv Exp Med Biol. 2017;1024:133-151. doi:10.1007/978-981-10-5987-2_6. PMID: 28921468.

20. Yue Xing^#, Xiaomin Yao^#, Hua Li, Guang Xue, Qiuhong Guo, Guiwen Yang, Ailing Lu, Yan Zhang, Guangxun Meng^*, Cutting Edge: TRAF6 Mediates TLR/IL-1R Signaling-Induced Nontranscriptional Priming of the NLRP3 Inflammasome, J Immunology, 2017 Sep 1;199(5):1561-1566. doi: 10.4049/jimmunol.1700175. PMID:28739881.

21. Rongrong Ren^#, Shuxian Wu^#, Jialin Cai^#, Yuqin Yang^#, Xiaonan Ren, Yanling Feng, Lixiang Chen, Boyin Qin, Chunhua Xu, Hua Yang, Zhigang Song, Di Tian, Yunwen Hu, Xiaohui Zhou* & Guangxun Meng^*.The H7N9 influenza A virus infection results in lethal inflammation in the mammalian host via the NLRP3-caspase-1 inflammasome. Scientific Reports. 2017 Aug 8;7(1):7625. doi: 10.1038/s41598-017-07384-5. PMID: 28790324.

22. Zheng Li^#,  Hongbin Wang^#, Yihui Chen, Junling Niu, Qiuhong Guo, Qibin Leng, Zhong Huang, Zhirui Deng, Guangxun Meng^*. Interleukin-18 protects mice from Enterovirus 71 infection, Cytokine. 2017.08.01. 96:132~137. doi: 10.1016/j.cyto.2017.04.002. PMID: 28399485.

23. Ailing Lu^#, Hua Li^#, Junling Niu, Shuxian Wu, Guang Xue, Xiaomin Yao, Qiuhong Guo, Nianhong Wan, Paride Abliz, Guiwen Yang, Liguo An, Guangxun Meng^*, Hyper-activation of the NLRP3 Inflammasome in Myeloid cells Leads to Severe Organ Damage in Experimental Lupus. J Immunology, 2017.02.01, 198(3):1119~1129. doi: 10.4049/jimmunol.1600659. PMID: 28039299.

2016：

24. Xuesong Sang^#, Hongbin Wang^#, Yihui Chen, Qiuhong Guo, Ailing Lu , Xiaoli Zhu, Guangxun Meng^*. Vitamin C inhibits the activation of the NLRP3 inflammasome by scavenging mitochondrial ROS. Inflammasome 2016; 2: 13–19. 

25. Numan Javed , Guang Xue1, Ailing Lu, Yue Xing, Yoichiro Iwakura, Hui Xiao, Hervé Lecoeur, Gerald F. Spaeth, Guangxun Meng^*. Cross reactivity of S. aureus to murine cytokine assays: A source of discrepancy. Cytokine 81 (2016) 101–108. doi: 10.1016/j.cyto.2016.03.007. PMID: 26978550.

2015： 

26. Mingkuan Chen, Yue Xing, Ailing Lu, Wei Fang, Bing Sun, Changbin Chen, Wanqing Liao, and Guangxun Meng^*, Internalized Cryptococcus neoformans Activates the Canonical Caspase-1 and the Noncanonical Caspase-8 Inflammasomes, J Immunology, 2015.11.15,195(10):4962~4972. doi: 10.4049/jimmunol.1500865. PMID: 26466953.

27. Hongbin Wang#, Xiaobo Lei#, Xia Xiao, Chunfu Yang, Wenli Lu, Zhong Huang,Qibin Leng,Qi Jin,Bin He, Guangxun Meng^*, and Jianwei Wang^*, Reciprocal Regulation between Enterovirus 71 and the NLRP3 Inflammasome, Cell Reports, 2015.7.7, 12(1): 42~48, SCIE. doi: 10.1016/j.celrep.2015.05.047. PMID: 26119741.

28. Liqiong Song^#, Yuanming Huang^#, Meng Zhao, Zhihao Wang, Shujing Wang, Hui Sun, Biao Kan, Guangxun Meng^*, Weili Liang^*, Zhihong Ren^*. A critical role for hemolysin in Vibrio fluvialis-induced IL-1β secretion mediated by the NLRP3 inflammasome in macrophages. Front Microbiol. 2015 May 22;6:510. doi: 10.3389/fmicb.2015.00510. PMID: 26052324.

2014： 

29. Caiqin Guo ^#, Mingkuan Chen^#, Zhenzong Fa, Ailing Lu, Wei Fang, Bing Sun, Changbin Chen , Wanqing Liao^*, Guangxun Meng^*, Acapsular Cryptococcus neoformans activates the NLRP3 inflammasome. Microbes and Infection. 2014 Oct;16(10):845-54.doi: 10.1016/j.micinf.2014.08.013. PMID: 25193031.

30. Liming Mao^#, Liping Zhang^#, Hua Li^#, Wei Chen, Hongbin Wang, Shuxian Wu, Caiqin Guo, Ailing Lu, Guiwen Yang, Liguo An, Paride Abliz* , Guangxun Meng*. Pathogenic Fungus Microsporum canis Activates the NLRP3 Inflammasome. INFECT IMMUN. 2014 Feb;82(2):882-92. doi: 10.1128/IAI.01097-13. PMID: 24478101.

31. Wei Chen ^#, Yongfen Xu ^#, Hua Li, Wanyin Tao, Yu Xiang, Bing Huang, Junqi Niu, Jin Zhong^*,Guangxun Meng^*. HCV Genomic RNA Activates the NLRP3 Inflammasome in Human Myeloid Cells. PLOS ONE. 2014 Jan 6;9(1):e84953. doi: 10.1371/journal.pone.0084953. PMID: 24400125.

2013： 

32. Yongfen Xu^#., Hua Li^#., Wei Chen^#., Xiaomin Yao, Yue Xing, Xun Wang, Jin Zhong^*,Guangxun Meng^*. Mycoplasma hyorhinis Activates the NLRP3 Inflammasome and Promotes Migration and Invasion of Gastric Cancer Cells. PLOS ONE. 2013 Nov 6;8(11):e77955.doi: 10.1371/journal.pone.0077955. PMID: 24223129.

33. Hongbin Wang, Liming Mao, Guangxun Meng^*. The NLRP3 inflammasome activation in human or mouse cells, sensitivity causes puzzle. Protein Cell. 2013 Aug;4(8):565-8. doi: 10.1007/s13238-013-3905-0. PMID: 23794000.

34. Guowei Lei^#, Mingkuan Chen^#, Hua Li^#, Junling Niu, Shuxian Wu, Liming Mao, Ailing Lu, Hongbin Wang, Wei Chen, Bin Xu, Qibin Leng, Cunshuan Xu, Guiwen Yang, Liguo An, Liping Zhu^*, Guangxun Meng^*. Biofilm from a clinical strain of Cryptococcus neoformans activates the NLRP3 inflammasome. Cell Research. 2013 Jul;23(7):965-8. doi: 10.1038/cr.2013.49. PMID: 23567555.

35. Hua Li^#, Shuxian Wu^#, Liming Mao^#, Guowei Lei, Liping Zhang, Ailing Lu, Liguo An,Guiwen Yang, Paride Abliz^*, Guangxun Meng^*. Human pathogenic fungus Trichophyton schoenleinii activates the NLRP3 inflammasome. Protein Cell. 2013 Jul;4(7):529-38. doi: 10.1007/s13238-013-2127-9. PMID: 23686720.

36. Yan Wang^#, Chen Yang^#, Kairui Mao, Shuzhen Chen, Guangxun Meng^*, Bing Sun^*. Cellular localization of NLRP3 inflammasome. Protein Cell. 2013 Jun;4(6):425-31. doi: 10.1007/s13238-013-2113-2. PMID: 23609011.

37. Hongbin Wang, Yue Xing, Liming Mao, Yi Luo, Lishan Kang, Guangxun Meng*. Pannexin-1 influences peritoneal cavity cell population but is not involved in NLRP3 inflammasome activation. Protein Cell. 2013 Apr;4(4):259-65. doi: 10.1007/s13238-013-2114-1. PMID: 23549611.

38. Kairui Mao^#, Shuzhen Chen^#, Mingkuan Chen, Yonglei Ma, Yan Wang, Bo Huang, Zhengyu He, Yan Zeng, Yu Hu, Shuhui Sun, Jing Li, Xiaodong Wu, Xiangrui Wang, Warren Strober, Chang Chen,Guangxun Meng*, Bing Sun*. Nitric oxide suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock. Cell Research. 2013 Feb; 23(2):201-12.doi: 10.1038/cr.2013.6. PMID: 23318584.

Principal Investigator: MENG Guangxun

Senior Technician: GUO Qiuhong

Assistant Professors: CHEN Mengdan, LI Juan, CUI Mengmeng

Research Assistant: GAO Yuhui

Post-Doctoral Fellows: NIU Junling, SHEN Junchen

Ph.D. Students: ZHANG Yu, ZHENG Xu, LI Jiaxun

M.S. Students: ZOU Hongyuan, LIU Jia (rotation)

Co-supervised M.S. Student: DUAN Dong (Soochow University)