IL-15 Links TLR2/1-Induced Macrophage Differentiation to the Vitamin D-Dependent Antimicrobial Pathway

被引：169

作者：

Krutzik, Stephan R.

Hewison, Martin ^{[2
]}

Liu, Philip T.

Robles, Juan Antonio

Stenger, Steffen ^{[4
]}

Adams, John S. ^{[2
]}

Modlin, Robert L. ^{[1
,3
]}

机构：

[1] Univ Calif Los Angeles, Div Dermatol, David Geffen Sch Med, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Orthopaed Hosp, Dept Orthoped Surg, Los Angeles, CA 90024 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol & Immunol, Los Angeles, CA 90095 USA

[4] Univ Hosp, Inst Clin Microbiol & Hyg, Ulm, Germany

来源：

JOURNAL OF IMMUNOLOGY | 2008年 / 181卷 / 10期

关键词：

D O I：

10.4049/jimmunol.181.10.7115

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

An essential function of the innate immune system is to directly trigger antimicrobial mechanisms to defend against invading pathogens. In humans, one such pathway involves activation by TLR2/IL leading to the vitamin D-dependent induction of antimicrobial peptides. In this study, we found that TLR2/1-induced IL-15 was required for induction of CYP27b1, the VDR and the downstream antimicrobial peptide cathelicidin. Although both IL-15 and IL-4 triggered macrophage differentiation, only IL-15 was sufficient by itself to induce CYP27b1 and subsequent bioconversion of 25-hydroxyvitamin D3 (25D3) into bioactive 1,25D3, leading to VDR activation and induction of cathelicidin. Finally, IL-15-differentiated macrophages could be triggered by 25D3 to induce an antimicrobial activity against intracellular Mycobacterium tuberculosis. Therefore, IL-15 links TLR2/1-induced macrophage differentiation to the vitamin D-dependent antimicrobial pathway. The Journal of Imunology, 2008, 181: 7115-7120.

引用

页码：7115 / 7120

页数：6

共 38 条

[31] Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase [J].