Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement.
Cells lining the gastrointestinal tract serve as both a barrier to and a pathway for infectious agent entry. Dendritic cells (DCs) present in the lamina propria under the columnar villus epithelium of the small bowel extend processes across this epithelium and capture bacteria, but previous studies provided limited information on the nature of the stimuli, receptors, and signaling events involved in promoting this phenomenon. Here, we use immunohistochemical as well as dynamic explant and intravital two-photon imaging to investigate this issue. Analysis of CD11c-enhanced green fluorescent protein (EGFP) or major histocompatibility complex CII-EGFP mice revealed that the number of trans-epithelial DC extensions, many with an unusual "balloon" shape, varies along the length of the small bowel. High numbers of such extensions were found in the proximal jejunum, but only a few were present in the terminal ileum. The extensions in the terminal ileum markedly increased upon the introduction of invasive or noninvasive Salmonella organisms, and chimeric mouse studies revealed the key role of MyD88-dependent Toll-like receptor (TLR) signaling by nonhematopoietic (epithelial) elements in the DC extension response. Collectively, these findings support a model in which epithelial cell TLR signaling upon exposure to microbial stimuli induces active DC sampling of the gut lumen at sites distant from organized lymphoid tissues.
Chieppa
Marcello
M
Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Rescigno
Maria
M
Huang
Alex Y C
AY
Germain
Ronald N
RN
D000818:Animals; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D022081:Cell Surface Extensions / Q000187:drug effects / Q000502:physiology*; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000382:microbiology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology*; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D047569:Laser Scanning Cytometry; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011135:Polysaccharides, Bacterial / Q000494:pharmacology; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D012480:Salmonella Infections / Q000276:immunology / Q000382:microbiology; D012486:Salmonella typhimurium / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists / Q000502:physiology*
C493447:CCL20 protein, mouse; D039521:CD11c Antigen; D000073883:CX3C Chemokine Receptor 1; D054418:Chemokine CCL20; D019742:Chemokines, CC; C471885:Cx3cr1 protein, mouse; D000949:Histocompatibility Antigens Class II; D019402:Macrophage Inflammatory Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009838:Oligodeoxyribonucleotides; D011135:Polysaccharides, Bacterial; D019707:Receptors, Chemokine; D051193:Toll-Like Receptors; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins