CCL17-expressing dendritic cells in the intestine are preferentially infected by Salmonella but CCL17 plays a redundant role in systemic dissemination.

Anna B Erazo,Nancy Wang,Irmgard Förster,Heike Weighardt,Richard A Strugnell,Adrian D Semeniuk,Sevgi C Cengiz,Lorenz Fülle,Lena Standke,Manja Thiem

doi:10.1002/iid3.445

Abstract

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.MethodsWT, 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.ResultsHistological 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.ConclusionCCL17‐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.

Highlights

Salmonella spp. are a recognized and global cause of serious health issues from gastroenteritis to invasive disease
In mesenteric lymph nodes (mLNs), serovar Typhimurium (STM) were preferentially located within CCL17+ rather than CCL17− dendritic cells (DCs), besides other mononuclear phagocytes, and identified the CD103+ CD11b− DC subset as the main STM‐carrying DC population in the intestine
CCL17‐expressing DCs were preferentially infected by Salmonella in the intestine in comparison to other DC

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. Non‐typhoidal Salmonella serovars such as S. enterica serovar Typhimurium (STM) and serovar Enteritidis (STE) are a frequent cause of gut‐associated gastroenteritis in developed countries.[2] More recently, a subset of STM and STE strains have been linked to invasive non‐ typhoidal Salmonellosis (iNTS) in sub‐Saharan Africa with 20%–25% mortality.[3,4,5] An experimental model of iNTS can be reproduced by oral infection of susceptible mouse strains with STM.[6]

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