Activation and Immune Regulation Mechanisms of PYHIN Family During Microbial Infection

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2022 Feb 11

PMID 35145495

Authors

Xiaojiao Fan

Lianying Jiao

Tengchuan Jin

Affiliations

Soon will be listed here.

Abstract

The innate immune system defenses against pathogen infections via patten-recognition receptors (PRRs). PRRs initiate immune responses by recognizing pathogen-associated molecular patterns (PAMPs), including peptidoglycan, lipopolysaccharide, and nucleic acids. Several nucleic acid sensors or families have been identified, such as RIG-I-like receptors (RLRs), Toll-like receptors (TLRs), cyclic GMP-AMP synthase (cGAS), and PYHIN family receptors. In recent years, the PYHIN family cytosolic DNA receptors have increased attention because of their important roles in initiating innate immune responses. The family members in humans include Absent in melanoma 2 (AIM2), IFN-γ inducible protein 16 (IFI16), interferon-inducible protein X (IFIX), and myeloid cell nuclear differentiation antigen (MNDA). The PYHIN family members are also identified in mice, including AIM2, p202, p203, p204, and p205. Herein, we summarize recent advances in understanding the activation and immune regulation mechanisms of the PYHIN family during microbial infection. Furthermore, structural characterizations of AIM2, IFI16, p202, and p204 provide more accurate insights into the signaling mechanisms of PYHIN family receptors. Overall, the molecular details will facilitate the development of reagents to defense against viral infections.

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References

Sauer J, Witte C, Zemansky J, Hanson B, Lauer P, Portnoy D . Listeria monocytogenes triggers AIM2-mediated pyroptosis upon infrequent bacteriolysis in the macrophage cytosol. Cell Host Microbe. 2010; 7(5):412-9. PMC: 2947455. DOI: 10.1016/j.chom.2010.04.004. View

Jin T, Xiao T . Activation and assembly of the inflammasomes through conserved protein domain families. Apoptosis. 2014; 20(2):151-6. PMC: 4364414. DOI: 10.1007/s10495-014-1053-5. View

Conrady C, Zheng M, Fitzgerald K, Liu C, Carr D . Resistance to HSV-1 infection in the epithelium resides with the novel innate sensor, IFI-16. Mucosal Immunol. 2012; 5(2):173-83. PMC: 3288395. DOI: 10.1038/mi.2011.63. View

Gariano G, DellOste V, Bronzini M, Gatti D, Luganini A, De Andrea M . The intracellular DNA sensor IFI16 gene acts as restriction factor for human cytomegalovirus replication. PLoS Pathog. 2012; 8(1):e1002498. PMC: 3266931. DOI: 10.1371/journal.ppat.1002498. View

Diner B, Lum K, Toettcher J, Cristea I . Viral DNA Sensors IFI16 and Cyclic GMP-AMP Synthase Possess Distinct Functions in Regulating Viral Gene Expression, Immune Defenses, and Apoptotic Responses during Herpesvirus Infection. mBio. 2016; 7(6). PMC: 5111403. DOI: 10.1128/mBio.01553-16. View

Storek K, Gertsvolf N, Ohlson M, Monack D . cGAS and Ifi204 cooperate to produce type I IFNs in response to Francisella infection. J Immunol. 2015; 194(7):3236-45. PMC: 4367159. DOI: 10.4049/jimmunol.1402764. View

Jones J, Kayagaki N, Broz P, Henry T, Newton K, ORourke K . Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis. Proc Natl Acad Sci U S A. 2010; 107(21):9771-6. PMC: 2906881. DOI: 10.1073/pnas.1003738107. View

Luan Y, Yu X, Xu K, Ding B, Yu J, Huang Y . The retinoblastoma protein is an essential mediator of osteogenesis that links the p204 protein to the Cbfa1 transcription factor thereby increasing its activity. J Biol Chem. 2007; 282(23):16860-70. DOI: 10.1074/jbc.M610943200. View

Gribaudo G, Riera L, Hertel L, Landolfo S . In vitro and in vivo expression analysis of the interferon-inducible 203 gene. J Interferon Cytokine Res. 1999; 19(2):129-36. DOI: 10.1089/107999099314270. View

10.

Chen I, Ou-Yang F, Hung J, Liu J, Wang H, Wang S . AIM2 suppresses human breast cancer cell proliferation in vitro and mammary tumor growth in a mouse model. Mol Cancer Ther. 2006; 5(1):1-7. DOI: 10.1158/1535-7163.MCT-05-0310. View

11.

Fang R, Tsuchiya K, Kawamura I, Shen Y, Hara H, Sakai S . Critical roles of ASC inflammasomes in caspase-1 activation and host innate resistance to Streptococcus pneumoniae infection. J Immunol. 2011; 187(9):4890-9. PMC: 3197964. DOI: 10.4049/jimmunol.1100381. View

12.

Sui H, Zhou M, Chen Q, Lane H, Imamichi T . siRNA enhances DNA-mediated interferon lambda-1 response through crosstalk between RIG-I and IFI16 signalling pathway. Nucleic Acids Res. 2013; 42(1):583-98. PMC: 3874163. DOI: 10.1093/nar/gkt844. View

13.

Cai H, Yan L, Liu N, Xu M, Cai H . IFI16 promotes cervical cancer progression by upregulating PD-L1 in immunomicroenvironment through STING-TBK1-NF-kB pathway. Biomed Pharmacother. 2020; 123:109790. DOI: 10.1016/j.biopha.2019.109790. View

14.

Chen W, Yu S, Zhou F, Zhang X, Gao W, Li K . DNA Sensor IFI204 Contributes to Host Defense Against Infection in Mice. Front Immunol. 2019; 10:474. PMC: 6431627. DOI: 10.3389/fimmu.2019.00474. View

15.

Zhu W, Liu P, Yu L, Chen Q, Liu Z, Yan K . p204-initiated innate antiviral response in mouse Leydig cells. Biol Reprod. 2014; 91(1):8. DOI: 10.1095/biolreprod.114.119396. View

16.

Luan Y, Lengyel P, Liu C . p204, a p200 family protein, as a multifunctional regulator of cell proliferation and differentiation. Cytokine Growth Factor Rev. 2008; 19(5-6):357-69. PMC: 4442486. DOI: 10.1016/j.cytogfr.2008.11.002. View

17.

Asefa B, Dermott J, Kaldis P, Stefanisko K, Garfinkel D, Keller J . p205, a potential tumor suppressor, inhibits cell proliferation via multiple pathways of cell cycle regulation. FEBS Lett. 2006; 580(5):1205-14. DOI: 10.1016/j.febslet.2006.01.032. View

18.

Lee S, Karki R, Wang Y, Nguyen L, Kalathur R, Kanneganti T . AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence. Nature. 2021; 597(7876):415-419. PMC: 8603942. DOI: 10.1038/s41586-021-03875-8. View

19.

Wichit S, Hamel R, Yainoy S, Gumpangseth N, Panich S, Phuadraksa T . Interferon-inducible protein (IFI) 16 regulates Chikungunya and Zika virus infection in human skin fibroblasts. EXCLI J. 2019; 18:467-476. PMC: 6694701. DOI: 10.17179/excli2019-1271. View

20.

Hafner-Bratkovic I, Susjan P, Lainscek D, Tapia-Abellan A, Cerovic K, Kadunc L . NLRP3 lacking the leucine-rich repeat domain can be fully activated via the canonical inflammasome pathway. Nat Commun. 2018; 9(1):5182. PMC: 6281599. DOI: 10.1038/s41467-018-07573-4. View