CCL17‐expressing dendritic cells in the intestine are preferentially infected by Salmonella but CCL17 plays a redundant role in systemic dissemination
Introduction Salmonella spp. are a recognized and global cause of serious health issues from gastroenteritis to invasive disease. The mouse model of human typhoid fever, which uses Salmonella enterica serovar Typhimurium (STM) in susceptible mouse strains, has revealed that the bacteria gain access...
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| Published in: | Immunity, Inflammation and Disease Vol. 9; no. 3; pp. 891 - 904 |
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| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
England
John Wiley & Sons, Inc
01-09-2021
John Wiley and Sons Inc Wiley |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Introduction
Salmonella spp. are a recognized and global cause of serious health issues from gastroenteritis to invasive disease. The mouse model of human typhoid fever, which uses Salmonella enterica serovar Typhimurium (STM) in susceptible mouse strains, has revealed that the bacteria gain access to extraintestinal tissues from the gastrointestinal tract to cause severe systemic disease. Previous analysis of the immune responses against Salmonella spp. revealed the crucial role played by dendritic cells (DCs) in carrying STM from the intestinal mucosa to the mesenteric lymph nodes (mLNs), a key site for antigen presentation and T cell activation. In this study, we investigated the influence of chemokine CCL17 on the dissemination of STM.
Methods
WT, CCL17/EGFP reporter, or CCL17‐deficient mice were infected orally with STM (SL1344) or mCherry‐expressing STM for 1–3 days. Colocalization of STM with CCL17‐expressing DCs in Peyer's patches (PP) and mLN was analyzed by fluorescence microscopy. In addition, DCs and myeloid cell populations from naïve and Salmonella‐infected mice were analyzed by flow cytometry. Bacterial load was determined in PP, mLN, spleen, and liver 1 and 3 days after infection.
Results
Histological analysis revealed that CCL17‐expressing cells are located in close proximity to STM in the dome area of PP. We show that, in mLN, STM were preferentially located within CCL17+ rather than CCL17− DCs, besides other mononuclear phagocytes, and identified the CD103+ CD11b− DC subset as the main STM‐carrying DC population in the intestine. STM infection triggered upregulation of CCL17 expression in specific intestinal DC subsets in a tissue‐specific manner. The dissemination of STM from the gut to the mLN, however, was only moderately influenced by the presence of CCL17.
Conclusion
CCL17‐expressing DCs were preferentially infected by Salmonella in the intestine in comparison to other DC. Nevertheless, the production of CCL17 was not essential for the early dissemination of Salmonella from the gut to systemic organs.
Oral infection with Salmonella enhances the frequency of dendritic cells expressing the pro‐inflammatory chemokine CCL17, promoting dendritic cell–T cell interaction. In Peyer's patches, CCL17‐expressing cells colocalize with Salmonella and Salmonella‐containing cells in mesenteric lymph nodes are preferentially CCL17‐positive. While CCL17‐expressing cells participate in the early dissemination of Salmonella, CCL17 itself appears to play a redundant role in this process. |
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| Bibliography: | Anna B. Erazo and Nancy Wang should be considered joint first authors. Richard A. Strugnell and Irmgard Förster should be considered joint senior authors. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 2050-4527 2050-4527 |
| DOI: | 10.1002/iid3.445 |