CD38 Controls the Innate Immune Response against Listeria monocytogenes
CD38 Controls the Innate Immune Response against Listeria monocytogenes
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DOI：
10.1128/iai.00340-13
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发表时间：
2013-11-01
影响因子：
3.1
通讯作者：
Mittruecker, Hans-Willi
中科院分区：
文献类型：
--
作者：
Lischke, Timo;Heesch, Kira;Mittruecker, Hans-Willi
CD38（腺苷-5'-二磷酸-核糖基环化酶 1）是一种多功能酶，在多种细胞类型中表达。 CD38 被赋予多种功能，包括产生钙动员代谢物、细胞活化和趋化性。使用小鼠单核细胞增生李斯特氏菌感染模型，我们发现 CD38 敲除 (KO) 小鼠非常容易受到感染。感染后 3 天内易感性增强就已经很明显，表明 CD38 在先天免疫反应中发挥作用。 CD38在中性粒细胞和炎症单核细胞上表达，特别是炎症单核细胞在感染过程中进一步上调CD38。 CD38 的缺失导致两种细胞类型向感染部位的迁移模式发生改变。我们观察到脾脏中的细胞积累受损，但肝脏中的细胞积累惊人地相似甚至更高。 CD38 KO 和野生型小鼠在血液和骨髓中的中性粒细胞和炎性单核细胞的组成方面显示出类似的变化，表明这些细胞从骨髓的动员是不依赖于 CD38 的。在体外，CD38 KO小鼠的巨噬细胞摄取李斯特菌的效率较低，但仍然能够杀死细菌。树突状细胞在感染后也表现出增强的 CD38 表达。然而，CD38的缺失并不会损害小鼠启动CD8+T细胞对抗单核细胞增生李斯特菌的能力，并且CD38 KO小鼠可以有效控制继发性李斯特菌感染。总之，我们的结果证明 CD38 在针对单核细胞增生李斯特菌的先天免疫反应中发挥着重要作用。
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.