Infection 2013-5

 

CD38 controls the innate immune response against Listeria monocytogenes.

Infect Immun. 2013 Aug 26.

Lischke T, Heesch K, Schumacher V, Schneider M, Haag F, Koch-Nolte F, Mittrücker HW.

Institute of Immunology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, D-20251 Hamburg, Germany.

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 KO mice were highly susceptible to infection. Enhanced susceptibility was already evident within three 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 WT 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.

PMID: 23980105 [PubMed – as supplied by publisher]

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