Differential expansion, activation and effector functions of conventional and plasmacytoid dendritic cells in mouse tissues transiently infected with Listeria monocytogenes.
Dendritic cells (DC) are crucial in generating immunity to infection. Here we characterize changes in DC in terms of number, activation and effector functions, focusing on conventional DC (cDC) and plasmacytoid DC (pDC), in Listeria-infected mice. Kinetic studies showed a subset- and tissue-specific expansion of cDC and upregulation of CD80 and CD86 on splenic and mesenteric lymph node (MLN) cDC after intragastric infection. Expansion of pDC was more prolonged than cDC, and pDC upregulated CD86 and MHC-II, but not CD80, in both the spleen and MLN. cDC were an important source of IL-12 but not TNF-alpha during infection, while pDC made neither of these cytokines. Instead other CD11c(int) cells produced these cytokines. Using five-colour flow cytometry and double intracellular cytokine staining, we detected phenotypically similar CD11c(int)CD11b(+)Gr1(+) cells with distinct capacities to produce TNF-alpha/IL-12 or TNF-alpha/iNOS (inducible nitric oxide synthase) in Listeria-infected tissues. IL-12p70 was also produced by sorted CD11c(hi) and CD11c(int)CD11b(+)Gr1(+) cells. Furthermore, production of TNF-alpha, iNOS and IL-12 was differentially dependent on cellular localization of the bacteria. Cytosol-restricted bacteria induced TNF-alpha and iNOS-producing cells, albeit at lower frequency than wild-type bacteria. In contrast, IL-12 was induced only with wild-type bacteria. These data provide new insight into the relative abundance and function of distinct CD11c-expressing populations during the early stage of Listeria infection.
Tam
Miguel A
MA
Department of Clinical Immunology, Göteborg University, Göteborg, Sweden.
Wick
Mary Jo
MJ
D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics; D001427:Bacterial Toxins / Q000235:genetics; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006360:Heat-Shock Proteins / Q000235:genetics; D006460:Hemolysin Proteins; D018664:Interleukin-12 / Q000096:biosynthesis / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D007700:Kinetics; D008089:Listeria monocytogenes / Q000235:genetics / Q000502:physiology*; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology; D008198:Lymph Nodes / Q000166:cytology / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics; D008643:Mesentery / Q000166:cytology / Q000382:microbiology; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D021122:Protein Subunits / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C497965:Cd86 protein, mouse; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D053762:Interleukin-12 Subunit p40; D008565:Membrane Proteins; D021122:Protein Subunits; D014409:Tumor Necrosis Factor-alpha; C072980:actA protein, Listeria monocytogenes; D018664:Interleukin-12; D052247:Nitric Oxide Synthase Type II; C038705:hlyA protein, Listeria monocytogenes