title: Interleukin-12-producing CD103+ CD11b- CD8+ dendritic cells are responsible for eliciting gut intraepithelial lymphocyte response against Encephalitozoon cuniculi.
abstract: Microsporidia, which belong to the kingdom Fungi, are important opportunistic pathogens in HIV-infected populations and organ transplant recipients that are often associated with a broad range of symptoms, such as diarrhea, nephritis, and encephalitis. Natural infection occurs via the oral route, and as a consequence, gut immunity plays an important role in restricting the dissemination of these pathogens. Studies from our laboratory have reported that the pathogens induce a rapid intraepithelial lymphocyte (IEL) response important for host protection. Although mucosal dendritic cells (DC) are likely involved in triggering an antigen-specific IEL response, the specific subset(s) responsible has yet to be identified. Toward this goal, we demonstrate a very important role for mucosal CD11b(-) CD8(+) DC in the initiation of an antigen-specific IEL in vivo. Effectively, after Encephalitozoon cuniculi infection, CD11b(-) CD8(+) DC were activated in the lamina propria (LP) and acquired the ability to process retinoic acid (RA). However, this subset did not produce interleukin 12 (IL-12) but upregulated CD103, which is essential for migration to the mesenteric lymph nodes (MLN). Interestingly, CD103(+) CD11b(-) CD8(+) DC in the MLN, in addition to processing RA, also secreted IL-12 and were responsible for gut imprinting specificity on mucosal CD8 T cells. To the best of our knowledge, this is the first report describing the importance of MLN CD103(+) CD11b(-) CD8(+) DC isolated from infected animals in the generation of an IEL response against a live pathogen.
authors.affiliation: Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC, USA.
authors.forename: Magali M
authors.initials: MM
authors.lastname: Moretto
authors.affiliation: Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC, USA.
authors.forename: Danielle I
authors.initials: DI
authors.lastname: Harrow
authors.affiliation: Flow Cytometry Core Facility, George Washington University, Washington, DC, USA.
authors.forename: Teresa S
authors.initials: TS
authors.lastname: Hawley
authors.affiliation: Department of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC, USA imti56@gwu.edu.
authors.forename: Imtiaz A
authors.initials: IA
authors.lastname: Khan
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D009670:Encephalitozoon cuniculi / Q000276:immunology* / Q000472:pathogenicity; D016890:Encephalitozoonosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions; D018928:Immunity, Mucosal; D016130:Immunophenotyping; D039001:Integrin alpha Chains / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D007422:Intestines / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008164:Luminescent Proteins / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; D001426:Bacterial Proteins; D039481:CD11b Antigen; D039001:Integrin alpha Chains; D008164:Luminescent Proteins; C091367:alpha E integrins; C054562:yellow fluorescent protein, Bacteria; D049452:Green Fluorescent Proteins; D018664:Interleukin-12