CD38 controls the innate immune response against Listeria monocytogenes

TY - JOUR

T1 - CD38 controls the innate immune response against Listeria monocytogenes

AU - Lischke, Timo

AU - Heesch, Kira

AU - Schumacher, Valéa

AU - Schneider, Michael

AU - Haag, Friedrich

AU - Nolte, Friedrich

AU - Mittrücker, Hans-Willi

PY - 2013/11/1

Y1 - 2013/11/1

N2 - 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.

AB - 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.

KW - Animals

KW - Antigens, CD38

KW - Cell Movement

KW - Dendritic Cells

KW - Disease Models, Animal

KW - Disease Susceptibility

KW - Gene Deletion

KW - Host-Pathogen Interactions

KW - Immunity, Innate

KW - Listeria monocytogenes

KW - Listeriosis

KW - Liver

KW - Macrophages

KW - Membrane Glycoproteins

KW - Mice

KW - Mice, Knockout

KW - Monocytes

KW - Neutrophils

KW - Phagocytosis

KW - Spleen

U2 - 10.1128/IAI.00340-13

DO - 10.1128/IAI.00340-13

M3 - SCORING: Journal article

C2 - 23980105

VL - 81

SP - 4091

EP - 4099

JO - INFECT IMMUN

JF - INFECT IMMUN

SN - 0019-9567

IS - 11

ER -