Silk fibroin hydrogel as mucosal vaccine carrier: induction of gastric CD4+TRM cells mediated by inflammatory response induces optimal immune protection against Helicobacter felis

Chupeng Hu; Wei Liu; Ningyin Xu; An Huang; Zhenxing Zhang; Menghui Fan; Guojing Ruan; Yue Wang; Tao Xi; Yingying Xing

doi:10.1080/22221751.2020.1830719

Silk fibroin hydrogel as mucosal vaccine carrier: induction of gastric CD4+TRM cells mediated by inflammatory response induces optimal immune protection against Helicobacter felis

Emerg Microbes Infect. 2020 Dec;9(1):2289-2302. doi: 10.1080/22221751.2020.1830719.

Authors

Chupeng Hu^{1

2}, Wei Liu^{1

2}, Ningyin Xu^{1

2}, An Huang^{1

2}, Zhenxing Zhang^{1

2}, Menghui Fan^{1

2}, Guojing Ruan^{1

2}, Yue Wang^{1

2}, Tao Xi^{1

2}, Yingying Xing^{1

2}

Affiliations

¹ School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.
² Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China.

Abstract

Tissue-resident memory T (T_RM) cells, located in the epithelium of most peripheral tissues, constitute the first-line defense against pathogen infections. Our previous study reported that gastric subserous layer (GSL) vaccination induced a "pool" of protective tissue-resident memory CD4+T (CD4+T_RM) cells in the gastric epithelium. However, the mechanistic details how CD4+T_RM cells form in the gastric epithelium are unknown. Here, our results suggested that the vaccine containing CCF in combination with Silk fibroin hydrogel (SF) broadened the distribution of gastric intraepithelial CD4+T_RM cells. It was revealed that the gastric intraepithelial T_RM cells were even more important than circulating memory T cells against infection by Helicobacter felis. It was also shown that gastric-infiltrating neutrophils were involved as indispensable mediators which secreted CXCL10 to chemoattract CXCR3+CD4+T cells into the gastric epithelium. Blocking of CXCR3 or neutrophils significantly decreased the number of gastric intraepithelial CD4+T_RM cells due to reduced recruitment of CD4+T cells. This study demonstrated the protective efficacy of gastric CD4+T_RM cells against H. felis infection, and highlighted the influence of neutrophils on gastric intraepithelial CD4+T_RM cells formation.

Keywords: Helicobacter felis; CXCR3; Gastric intraepithelial CD4+TRM cells; neutrophils; silk fibroin hydrogel.

MeSH terms

Animals
Bacterial Vaccines
CD4-Positive T-Lymphocytes / metabolism*
CD8-Positive T-Lymphocytes / metabolism
Chemokine CXCL10 / genetics
Fibroins / administration & dosage*
Fibroins / chemistry
Fibroins / immunology
Gastric Mucosa / immunology
Helicobacter Infections / genetics
Helicobacter Infections / immunology
Helicobacter Infections / prevention & control*
Helicobacter felis / immunology*
Hydrogels
Immunologic Memory
Mice
Neutrophils / metabolism
Receptors, CXCR3 / genetics

Substances

Bacterial Vaccines
Chemokine CXCL10
Cxcl10 protein, mouse
Cxcr3 protein, mouse
Hydrogels
Receptors, CXCR3
Fibroins

Grants and funding

This work was supported by National Natural Science Foundation of China (No. 81971562), National Key Research and Development Project (No. 2017YFD0400303), Postgraduate Research & Practice Innovation Program of Jiangsu Province, The Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions, Six Talent Peaks Project in Jiangsu Province (No. 2018-WSW-003).