Luminal Bacteria Recruit CD103+ Dendritic Cells into the Intestinal Epithelium to Sample Bacterial Antigens for Presentation

• Published in: Immunity (Cambridge, Mass.) Vol. 38; no. 3; pp. 581 - 595
• Main Authors: Farache, Julia, Koren, Idan, Milo, Idan, Gurevich, Irina, Kim, Ki-Wook, Zigmond, Ehud, Furtado, Glaucia C., Lira, Sergio A., Shakhar, Guy
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.03.2013; Elsevier Limited
• Subjects: Animals; Antigen Presentation - immunology; Antigens, Bacterial - immunology; Antigens, CD - immunology; Antigens, CD - metabolism; Bacteria; Behavior; Bone marrow; CD11c Antigen - genetics; CD11c Antigen - immunology; CD11c Antigen - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Line, Tumor; Cell Movement - immunology; Cells, Cultured; CX3C Chemokine Receptor 1; Dendritic Cells - immunology; Dendritic Cells - metabolism; Flow Cytometry; Host-Pathogen Interactions - immunology; Integrin alpha Chains - immunology; Integrin alpha Chains - metabolism; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestinal Mucosa - microbiology; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy; Microscopy, Fluorescence, Multiphoton; Morphology; Motility; Mucous Membrane - immunology; Mucous Membrane - metabolism; Mucous Membrane - microbiology; Receptors, Chemokine - genetics; Receptors, Chemokine - immunology; Receptors, Chemokine - metabolism; Salmonella; Salmonella typhi - immunology; Salmonella typhi - physiology; Salmonella typhimurium - immunology; Salmonella typhimurium - physiology; Toll-Like Receptors - immunology; Toll-Like Receptors - metabolism
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2013.01.009

CD103+ dendritic cells (DCs) carry bacteria from the small intestine and can present antigens to T cells. Yet they have not been recorded sampling luminal bacteria or presenting bacterial antigens in mesentery lymph nodes. We used 2-photon microscopy in live Cx3cr1+/gfp ×Cd11c-YFP mice to study these processes. At steady state, sparse CD103+ DCs occupied the epithelium. They patrolled among enterocytes while extending dendrites toward the lumen, likely using tight-junction proteins to penetrate the epithelium. Challenge with Salmonella triggered chemokine- and toll-like receptor (TLR)-dependent recruitment of additional DCs from the lamina propria (LP). The DCs efficiently phagocytosed the bacteria using intraepithelial dendrites. Noninvasive bacteria were similarly sampled. In contrast, CD103+ DCs sampled soluble luminal antigen inefficiently. In mice harboring CD103+ DCs, antigen-specific CD8 T cells were subsequently activated in MLNs. Intestinal CD103+ DCs are therefore equipped with unique mechanisms to independently complete the processes of uptake, transportation, and presentation of bacterial antigens. ► CD103+ DCs patrol the epithelium of the small intestine ► Salmonella infection recruits more DCs in a TLR and chemokine-dependent manner ► The DCs efficiently phagocytose salmonella using intraepithelial dendrites ► Soluble luminal antigens are sampled more efficiently by CX3CR1+ macrophages