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.

Application of Biomimetic Cell-Derived Nanoparticles with Mannose Modification as a Novel Vaccine Delivery Platform against Teleost Fish Viral Disease

“…APCs play an important role in initiating and regulating immune responses. Once antigens have more opportunities to be captured, processed, and presented by APCs, stronger immune response would be induced. , To enhance the internalization of NPs by APCs, different ligands were used to modify the surface of NPs. Owing to the high expression of mannose receptors on APCs, mannose is commonly used for the surface modification of nanocarriers. , Therefore, we modified the CS-G@M with mannose, which could specifically recognize the mannose receptor on teleost APCs.…”

Gastroprotective Mechanisms

“…After the gastric injury, there is an increase in the count of circulating neutrophils and a reduction in lymphocytes; the count of these cells or others that are part of the immune system are markers for GU [54,71]. In a recent study for the development of vaccines against the pathogen Helicobacter felis, an infiltration of the antibody Gr-1 in the stomach induced an inflammatory response that led to the formation of CD4+ memory T cells (TRM) essential for protection [105].…”