Escherichia coli adhesion protein FimH exacerbates colitis via CD11b+CD103- dendritic cell activation

Wei Zhang; Eun-Koung An; So-Jung Kim; Hae-Bin Park; Peter C W Lee; Jun-O Jin

doi:10.3389/fimmu.2023.1284770

Escherichia coli adhesion protein FimH exacerbates colitis via CD11b⁺CD103^- dendritic cell activation

Front Immunol. 2023 Nov 22:14:1284770. doi: 10.3389/fimmu.2023.1284770. eCollection 2023.

Authors

Wei Zhang¹, Eun-Koung An², So-Jung Kim², Hae-Bin Park², Peter C W Lee³, Jun-O Jin²

Affiliations

¹ Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai, China.
² Department of Microbiology, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
³ Department of Biochemistry and Molecular Biology, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Abstract

Introduction: Immune stimulators are used to improve vaccine efficiency; however, they are accompanied by various side effects. In previous studies, we reported that the Escherichia coli adhesion protein, FimH, induces immune activity; however, we did not examine any side effects in colon inflammation.

Methods: FimH was administered orally or intraperitoneally (i.p.) to mice with dextran sulfate sodium (DSS)-induced colitis, and changes in symptoms were observed. Immune cells infiltrated into the colon after the induction of colon inflammation were analyzed using a flow cytometer. Changes in Th1 and Th17 cells that induce colitis were analyzed. Further, mesenteric lymph node (mLN) dendritic cells (DCs) activated by FimH were identified and isolated to examine their ability to induce T-cell immunity.

Results: FimH oral and i.p. administration in C57BL/6 mice did not induce inflammation in the colon; however, DSS-induced colitis was exacerbated by oral and i.p. FimH administration. FimH treatment increased immune cell infiltration in the colon compared to that in DSS colitis. Th1 and Th17 cells, which are directly related to colitis, were increased in the colon by FimH; however, FimH did not directly affect the differentiation of these T cells. FimH upregulated the CD11b⁺CD103^- DC activity in the mLNs, which produced the signature cytokines required for Th1 and Th17. In addition, isolated CD11b⁺CD103^- DCs, after stimulation with FimH, directly induced Th1 and Th17 differentiation in a co-culture of CD4 T cells.

Conclusion: This study demonstrated the side effects of FimH and indicated that the use of FimH can aggravate the disease in patients with colitis.

Keywords: FimH; Th1; Th17; colitis; dendritic cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Colitis*
Dendritic Cells*
Humans
Inflammation / metabolism
Mice
Mice, Inbred C57BL

Substances

Itgam protein, mouse
alpha E integrins

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the Basic Research Program through the National Research Foundation of Korea (NRF), funded by MSIT (RS-2023-00207868) and a grant (2023IP0126) from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea. WZ was supported by the National Natural Science Foundation of China (82171830) and the Natural Science Foundation of Shanghai (21ZR1454200).