Impact of Toxoplasma gondii on Dendritic Cell Subset Function in the Intestinal Mucosa.
The function of mucosal dendritic cell (DC) subsets in immunity and inflammation is not well understood. In this study, we define four DC subsets present within the lamina propria and mesenteric lymph node compartments based on expression of CD103 and CD11b. Using IL-12p40 YFP (Yet40) reporter mice, we show that CD103(+)CD11b(-) mucosal DCs are primary in vivo sources of IL-12p40; we also identified CD103(-)CD11b(-) mucosal DCs as a novel population producing this cytokine. Infection was preferentially found in CD11b(+) DCs that were negative for CD103. Lamina propria DCs containing parasites were negative for IL-12p40. Instead, production of the cytokine was strictly a property of noninfected cells. We also show that vitamin A metabolism, as measured by ALDH activity, was preferentially found in CD103(+)CD11b(+) DC and was strongly downregulated in all mucosal DC subsets during infection. Finally, overall apoptosis of lamina propria DC subsets was increased during infection. Combined, these results highlight the ability of intestinal Toxoplasma infection to alter mucosal DC activity at both the whole population level and at the level of individual subsets.
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
Sara B
SB
Cohen
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853 eyd1@cornell.edu.
Eric Y
EY
Denkers
D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics; D039481:CD11b Antigen / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000469:parasitology; D015536:Down-Regulation; D005260:Female; D039001:Integrin alpha Chains / Q000096:biosynthesis; D050835:Interferon Regulatory Factors / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000235:genetics; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000469:parasitology; D007527:Isoenzymes / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology* / Q000469:parasitology; D014212:Tretinoin / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4
D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD; D001426:Bacterial Proteins; D039481:CD11b Antigen; D039001:Integrin alpha Chains; D050835:Interferon Regulatory Factors; D053762:Interleukin-12 Subunit p40; D007527:Isoenzymes; D008164:Luminescent Proteins; D050697:Retinal Dehydrogenase; D014212:Tretinoin; D014801:Vitamin A; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4; C091367:alpha E integrins; C054562:yellow fluorescent protein, Bacteria; C515028:ALDH1A1 protein, mouse