Pglyrp2-KO Mouse

Pglyrp2, or peptidoglycan recognition protein 2, is an innate immunity protein. It functions as an N-acetylmuramoyl-L-alanine amidase that hydrolyzes bacterial cell wall peptidoglycan. It is expressed in the liver and influences host-pathogen interactions, playing a role in antibacterial defenses and inflammatory responses [9].

In hepatocytes, Pglyrp2 acts as a pattern recognition receptor. Through phase separation, it can recognize and potentially eliminate covalently closed circular DNA of hepatitis B virus (HBV) in the nucleus, and suppress HBV capsid assembly by interacting with the viral capsid. Pathogenic variants or deletions in Pglyrp2 impair its ability to inhibit HBV replication, highlighting its role in hepatocyte-intrinsic immunity against HBV [1]. In the context of systemic lupus erythematosus (SLE), serum Pglyrp2 level is significantly increased and positively correlated with SLE disease activity index (SLEDAI), also being associated with renal damage and abnormal lipid profile parameters, suggesting its potential as a biomarker for SLE activity, dyslipidemia, and cardiovascular disease risks [2]. Regarding Parkinson's disease (PD), in the Chinese Han population, the rs892145 AT heterozygote of Pglyrp2 might increase the risk of PD and early-onset PD, and in Swedish PD patients, there was a sex-genotype interaction for rs892145 [3,6]. In oral epithelial cells, IL-36γ can stimulate Pglyrp2 gene expression, which is associated with oral mucosal homeostasis [4]. Also, Pglyrp2 along with sCD14 and FGA could be potential biomarkers for multidrug-resistant tuberculosis [5]. In hepatocellular carcinoma (HCC), Pglyrp2 is down-regulated, and its overexpression enhances antitumor immune responses [8]. In the developing brain, the absence of Pglyrp2 in knockout mice leads to alterations in the expression of the autism risk gene c-Met and sex-dependent changes in social behavior, suggesting its role in the gut-microbiota-brain communication [7].

In conclusion, Pglyrp2 has diverse functions in innate immunity, playing crucial roles in various disease conditions such as HBV infection, SLE, PD, oral mucosal homeostasis, multidrug-resistant tuberculosis, HCC, and brain development. The use of gene knockout mouse models has been instrumental in revealing these functions, providing insights into the underlying mechanisms and potential therapeutic targets for these diseases.

References:

1. Li, Ying, Ma, Huihui, Zhang, Yongjian, Yao, Yuanfei, Shi, Ming. 2025. PGLYRP2 drives hepatocyte-intrinsic innate immunity by trapping and clearing hepatitis B virus. In The Journal of clinical investigation, 135, . doi:10.1172/JCI188083. https://pubmed.ncbi.nlm.nih.gov/39946201/

2. Li, Hui, Meng, Defang, Jia, Jieting, Wei, Hua. 2021. PGLYRP2 as a novel biomarker for the activity and lipid metabolism of systemic lupus erythematosus. In Lipids in health and disease, 20, 95. doi:10.1186/s12944-021-01515-8. https://pubmed.ncbi.nlm.nih.gov/34461924/

3. Luan, Mengting, Jin, Jianing, Wang, Ying, Li, Xiaoyuan, Xie, Anmu. 2022. Association of PGLYRP2 gene polymorphism and sporadic Parkinson's disease in northern Chinese Han population. In Neuroscience letters, 775, 136547. doi:10.1016/j.neulet.2022.136547. https://pubmed.ncbi.nlm.nih.gov/35218888/

4. Scholz, Glen M, Heath, Jacqueline E, Aw, Jiamin, Reynolds, Eric C. 2018. Regulation of the Peptidoglycan Amidase PGLYRP2 in Epithelial Cells by Interleukin-36γ. In Infection and immunity, 86, . doi:10.1128/IAI.00384-18. https://pubmed.ncbi.nlm.nih.gov/29914927/

5. Chen, Jing, Han, Yu-Shuai, Yi, Wen-Jing, Jiang, Ting-Ting, Li, Ji-Cheng. 2020. Serum sCD14, PGLYRP2 and FGA as potential biomarkers for multidrug-resistant tuberculosis based on data-independent acquisition and targeted proteomics. In Journal of cellular and molecular medicine, 24, 12537-12549. doi:10.1111/jcmm.15796. https://pubmed.ncbi.nlm.nih.gov/32967043/

6. Ran, Caroline, Wirdefeldt, Karin, Sydow, Olof, Svenningsson, Per, Diaz Heijtz, Rochellys. 2023. Sex Differences in the Allele Distribution of PGLYRP2 Variant rs892145 in Parkinson's Disease. In Parkinson's disease, 2023, 6502727. doi:10.1155/2023/6502727. https://pubmed.ncbi.nlm.nih.gov/38106542/

7. Arentsen, T, Qian, Y, Gkotzis, S, Forssberg, H, Diaz Heijtz, R. 2016. The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior. In Molecular psychiatry, 22, 257-266. doi:10.1038/mp.2016.182. https://pubmed.ncbi.nlm.nih.gov/27843150/

8. Yang, Zongyi, Feng, Jia, Xiao, Li, Wu, Hongjin, Shi, Ming. 2020. Tumor-Derived Peptidoglycan Recognition Protein 2 Predicts Survival and Antitumor Immune Responses in Hepatocellular Carcinoma. In Hepatology (Baltimore, Md.), 71, 1626-1642. doi:10.1002/hep.30924. https://pubmed.ncbi.nlm.nih.gov/31479523/

9. Dziarski, Roman, Gupta, Dipika. 2010. Review: Mammalian peptidoglycan recognition proteins (PGRPs) in innate immunity. In Innate immunity, 16, 168-74. doi:10.1177/1753425910366059. https://pubmed.ncbi.nlm.nih.gov/20418257/