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

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:

• Gastric intraepithelial CD4+T_RM cells
• CXCR3
• Helicobacter felis
• silk fibroin hydrogel
• neutrophils

Acknowledgements

We thank Charlesworth Group (http://www.charlesworthauthorservices.com) and Dr. Xu for English language editing. Chupeng Hu carried out statistical analyses, participated in most experiments and drafted the manuscript. Wei Liu, Tao Xi and Yingying Xing conceived the study and participated in its design. Ningyin Xu, An Huang participated in the animal experiments. Zhenxing Zhang, Menghui Fan and Guojing Ruan participated in some animal experiments. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Availability of data and materials

All data generated or analysed during this study are included in this manuscript and its supplementary information files.

Additional information

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).