Mucosal vaccination increases local chemokine production attracting immune cells to the stomach mucosa of Helicobacter pylori infected mice

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• 作者：Carl-Fredrik Flach^a ; ^c ; Michael Mozer^a ; Malin Sundquist^a ; ^b ; Jan Holmgren^a ; ^c ; Sukanya Raghavan^a ; ^b ; ^{sukanya.raghavan@microbio.gu.se}
• 关键词：MadCAM-1 ; mucosal addressin cell adhesion molecule-1 ; Cag A ; Cytotoxin associated gene A ; VacA ; Vacuolating Cytotoxin ; CT ; cholera toxin ; STI ; Soyabean trypsin inhibitor
• 刊名：Vaccine
• 出版年：2012
• 出版时间：21 February 2012
• 年：2012
• 卷：30
• 期：9
• 页码：1636-1643
• 全文大小：406 K

文摘

Background

Vaccination is an attractive approach for the prevention of Helicobacter pylori infection and disease. In a mouse model, infection induces an accumulation of dendritic cells, macrophages, granulocytes, and B- and T cells to the stomach mucosa, which is further heightened when the infection is preceded by a mucosal immunization. We have studied the chemokines and chemokine receptors guiding infection- and vaccination-induced immune cells to the stomach and their relation to protection against H. pylori infection in mice.

Materials and methods

C57BL/6 mice were immunized sublingually with H. pylori lysate antigens and cholera toxin adjuvant or left unimmunized, and then challenged with live H. pylori bacteria. Stomach tissue was taken at 3, 7, 14 and 21 days after challenge and bacterial colonization, chemokine and chemokine receptor gene expression, and influx of cells into the stomach mucosa were evaluated.

Results

RT-PCR array screening revealed differential expression of a broad range of chemokine and chemokine receptor genes between immunized and unimmunized mice. A significant upregulation of chemokines known to attract, among other cells, eosinophils (CCL8), T cells (CXCL10, CXCL11) and neutrophils (CXCL2, CXCL5) and of their cognate receptors CCR3, CXCR3 and CXCR2, preceded or coincided with vaccine-induced protection, which was first evident 7 days after infection and was then sustained at the later time-points. Consistent with the increase in chemokines and chemokine receptors flow cytometric analysis indicated a sequential accumulation of CD4⁺ T cells, eosinophils, neutrophils and CD103⁺ dendritic cells in the gastric lamina propria of immunized mice.

Conclusions

This study provides insights into vaccination-induced chemokines that guide the influx of protective immune cells into the stomach of H. pylori infected mice.