title: CD38 controls the innate immune response against Listeria monocytogenes.
abstract: CD38, adenosine-5'-diphosphate-ribosyl cyclase 1, is a multifunctional enzyme, expressed on a wide variety of cell types. CD38 has been assigned diverse functions, including generation of calcium-mobilizing metabolites, cell activation, and chemotaxis. Using a murine Listeria monocytogenes infection model, we found that CD38 knockout (KO) mice were highly susceptible to infection. Enhanced susceptibility was already evident within 3 days of infection, suggesting a function of CD38 in the innate immune response. CD38 was expressed on neutrophils and inflammatory monocytes, and especially inflammatory monocytes further upregulated CD38 during infection. Absence of CD38 caused alterations of the migration pattern of both cell types to sites of infection. We observed impaired accumulation of cells in the spleen but surprisingly similar or even higher accumulation of cells in the liver. CD38 KO and wild-type mice showed similar changes in the composition of neutrophils and inflammatory monocytes in blood and bone marrow, indicating that mobilization of these cells from the bone marrow was CD38 independent. In vitro, macrophages of CD38 KO mice were less efficient in uptake of listeria but still able to kill the bacteria. Dendritic cells also displayed enhanced CD38 expression following infection. However, absence of CD38 did not impair the capacity of mice to prime CD8(+) T cells against L. monocytogenes, and CD38 KO mice could efficiently control secondary listeria infection. In conclusion, our results demonstrate an essential role for CD38 in the innate immune response against L. monocytogenes.
authors: Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Timo
authors: T
authors: Lischke
authors: Kira
authors: K
authors: Heesch
authors: Valéa
authors: V
authors: Schumacher
authors: Michael
authors: M
authors: Schneider
authors: Friedrich
authors: F
authors: Haag
authors: Friedrich
authors: F
authors: Koch-Nolte
authors: Hans-Willi
authors: HW
authors: Mittrücker
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000172:deficiency / Q000276:immunology*; D000818:Animals; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D017353:Gene Deletion; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000201:enzymology / Q000276:immunology; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology; D010587:Phagocytosis; D013154:Spleen / Q000276:immunology / Q000473:pathology
chemical_list: D008562:Membrane Glycoproteins; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1
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