Notch Signaling Regulates the Function and Phenotype of Dendritic Cells in Infection

Overview

Journal Microorganisms

Specialty Microbiology

Date 2023 Nov 25

PMID 38004829

Authors

Qiaoyuan Liu

Chuxi Chen

Yunxuan He

Wenhao Mai

Shipeng Ruan

Yunshan Ning

Yan Li

Affiliations

Soon will be listed here.

Abstract

Notch signaling manipulates the function and phenotype of dendritic cells (DCs), as well as the interaction between DCs and CD4 T cells. However, the role of Notch signaling in () infection remains elusive. Murine bone marrow-derived dendritic cells (BMDCs) were pretreated in the absence or presence of Notch signaling inhibitor DAPT prior to stimulation and the levels of Notch components, cytokines and surface markers as well as the differentiation of CD4 T cells in co-culture were measured using quantitative real-time PCR (qRT-PCR), Western blot, enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Compared with the control, the mRNA expression of all Notch receptors and Notch ligands Dll4 and Jagged1 was up-regulated in -stimulated BMDCs. The blockade of Notch signaling by DAPT influenced the production of IL-1β and IL-10 in -pulsed BMDCs, and reduced the expression of Notch1, Notch3, Notch4, Dll1, Dll3 and Jagged2. In addition, DAPT pretreatment decreased the expression of maturation markers CD80, CD83, CD86, and major histocompatibility complex class II (MHC-II) of BMDCs, and further skewed Th17/Treg balance toward Treg. Notch signaling regulates the function and phenotype of DCs, thus mediating the differentiation of CD4 T cells during infection.

Citing Articles

Helicobacter pylori and gastric cancer: mechanisms and new perspectives.

Duan Y, Xu Y, Dou Y, Xu D J Hematol Oncol. 2025; 18(1):10.

PMID: 39849657 PMC: 11756206. DOI: 10.1186/s13045-024-01654-2.

Global status and trends of gastric cancer and gastric microbiota research: a bibliometric analysis.

Ke Y, Tan C, Zhen J, Dong W Front Microbiol. 2024; 15:1341012.

PMID: 38655079 PMC: 11037409. DOI: 10.3389/fmicb.2024.1341012.

References

Fehlings M, Drobbe L, Moos V, Viveros P, Hagen J, Beigier-Bompadre M . Comparative analysis of the interaction of Helicobacter pylori with human dendritic cells, macrophages, and monocytes. Infect Immun. 2012; 80(8):2724-34. PMC: 3434561. DOI: 10.1128/IAI.00381-12. View

Kao J, Zhang M, Miller M, Mills J, Wang B, Liu M . Helicobacter pylori immune escape is mediated by dendritic cell-induced Treg skewing and Th17 suppression in mice. Gastroenterology. 2009; 138(3):1046-54. PMC: 2831148. DOI: 10.1053/j.gastro.2009.11.043. View

Hickey A, Stamou P, Udayan S, Ramon-Vazquez A, Esteban-Torres M, Bottacini F . Exopolysaccharide Blocks Dendritic Cell Maturation and Activation of CD4 T Cells. Front Microbiol. 2021; 12:653587. PMC: 8242212. DOI: 10.3389/fmicb.2021.653587. View

Helmin-Basa A, Wiese-Szadkowska M, Szaflarska-Poplawska A, Klosowski M, Januszewska M, Bodnar M . Relationship between Infection and Plasmacytoid and Myeloid Dendritic Cells in Peripheral Blood and Gastric Mucosa of Children. Mediators Inflamm. 2019; 2019:7190596. PMC: 6885256. DOI: 10.1155/2019/7190596. View

Lin C, Huang H, Hsieh C, Fan C, Lee Y . Jagged1-expressing adenovirus-infected dendritic cells induce expansion of Foxp3 regulatory T cells and alleviate T helper type 2-mediated allergic asthma in mice. Immunology. 2018; 156(2):199-212. PMC: 6328989. DOI: 10.1111/imm.13021. View

Ong C, Cheng H, Chang L, Ohtsuka T, Kageyama R, Stormo G . Target selectivity of vertebrate notch proteins. Collaboration between discrete domains and CSL-binding site architecture determines activation probability. J Biol Chem. 2005; 281(8):5106-19. DOI: 10.1074/jbc.M506108200. View

Ito T, Schaller M, Hogaboam C, Standiford T, Sandor M, Lukacs N . TLR9 regulates the mycobacteria-elicited pulmonary granulomatous immune response in mice through DC-derived Notch ligand delta-like 4. J Clin Invest. 2008; 119(1):33-46. PMC: 2613456. DOI: 10.1172/JCI35647. View

Hooi J, Lai W, Ng W, Suen M, Underwood F, Tanyingoh D . Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology. 2017; 153(2):420-429. DOI: 10.1053/j.gastro.2017.04.022. View

Higashi T, Hashimoto K, Takagi R, Mizuno Y, Okazaki Y, Tanaka Y . Curdlan induces DC-mediated Th17 polarization via Jagged1 activation in human dendritic cells. Allergol Int. 2010; 59(2):161-6. DOI: 10.2332/allergolint.09-OA-0103. View

10.

Lee C, Lin C, Leu S, Lee Y . Overexpression of Notch ligand Delta-like-1 by dendritic cells enhances their immunoregulatory capacity and exerts antiallergic effects on Th2-mediated allergic asthma in mice. Clin Immunol. 2017; 187:58-67. DOI: 10.1016/j.clim.2017.10.005. View

11.

Cao Q, Lu J, Kaur C, Sivakumar V, Li F, Cheah P . Expression of Notch-1 receptor and its ligands Jagged-1 and Delta-1 in amoeboid microglia in postnatal rat brain and murine BV-2 cells. Glia. 2008; 56(11):1224-37. DOI: 10.1002/glia.20692. View

12.

Amsen D, Helbig C, Backer R . Notch in T Cell Differentiation: All Things Considered. Trends Immunol. 2015; 36(12):802-814. DOI: 10.1016/j.it.2015.10.007. View

13.

Cheng P, Gabrilovich D . Notch signaling in differentiation and function of dendritic cells. Immunol Res. 2007; 41(1):1-14. PMC: 2709100. DOI: 10.1007/s12026-007-8011-z. View

14.

Rizzuti D, Ang M, Sokollik C, Wu T, Abdullah M, Greenfield L . Helicobacter pylori inhibits dendritic cell maturation via interleukin-10-mediated activation of the signal transducer and activator of transcription 3 pathway. J Innate Immun. 2014; 7(2):199-211. PMC: 6738898. DOI: 10.1159/000368232. View

15.

Gentle M, Rose A, Bugeon L, Dallman M . Noncanonical Notch signaling modulates cytokine responses of dendritic cells to inflammatory stimuli. J Immunol. 2012; 189(3):1274-84. PMC: 3442230. DOI: 10.4049/jimmunol.1103102. View

16.

Li Q, Zhang H, Yu L, Wu C, Luo X, Sun H . Down-regulation of Notch signaling pathway reverses the Th1/Th2 imbalance in tuberculosis patients. Int Immunopharmacol. 2017; 54:24-32. DOI: 10.1016/j.intimp.2017.10.026. View

17.

Skokos D, Nussenzweig M . CD8- DCs induce IL-12-independent Th1 differentiation through Delta 4 Notch-like ligand in response to bacterial LPS. J Exp Med. 2007; 204(7):1525-31. PMC: 2118646. DOI: 10.1084/jem.20062305. View

18.

Kao J, Rathinavelu S, Eaton K, Bai L, Zavros Y, Takami M . Helicobacter pylori-secreted factors inhibit dendritic cell IL-12 secretion: a mechanism of ineffective host defense. Am J Physiol Gastrointest Liver Physiol. 2006; 291(1):G73-81. DOI: 10.1152/ajpgi.00139.2005. View

19.

Andres S, Schmidt H, Mitchell H, Rhen M, Maeurer M, Engstrand L . Helicobacter pylori defines local immune response through interaction with dendritic cells. FEMS Immunol Med Microbiol. 2010; 61(2):168-78. DOI: 10.1111/j.1574-695X.2010.00761.x. View

20.

Owyang S, Zhang M, El-Zaatari M, Eaton K, Bishu S, Hou G . Dendritic cell-derived TGF-β mediates the induction of mucosal regulatory T-cell response to Helicobacter infection essential for maintenance of immune tolerance in mice. Helicobacter. 2020; 25(6):e12763. PMC: 7885176. DOI: 10.1111/hel.12763. View