1型干扰素（IFNα/β）和2型一氧化氮合酶调节对原生动物寄生虫的固有免疫反应。

Type 1 interferon (IFNalpha/beta) and type 2 nitric oxide synthase regulate the innate immune response to a protozoan parasite.

作者信息

Diefenbach A, Schindler H, Donhauser N, Lorenz E, Laskay T, MacMicking J, Röllinghoff M, Gresser I, Bogdan C

机构信息

Institute of Clinical Microbiology and Immunology, University of Erlangen, Germany.

出版信息

Immunity. 1998 Jan;8(1):77-87. doi: 10.1016/s1074-7613(00)80460-4.

DOI:10.1016/s1074-7613(00)80460-4

PMID:9462513

Abstract

Type 2 nitric oxide synthase (NOS2) is required for the Th1-dependent healing of infections with intracellular microbes, including Leishmania major. Here, we demonstrate the expression and define the function of NOS2 during the innate response to L. major. At day 1 of infection, genetic deletion or functional inactivation of NOS2 abolished the IFNgamma and natural killer cell response, increased the expression of TGFbeta, and caused parasite spreading from the skin and lymph node to the spleen, liver, bone marrow, and lung. Induction of NOS2 was dependent on IFNalpha/beta. Neutralization of IFNalpha/beta mimicked the phenotype of NOS2-/- mice. Thus, IFNalpha/beta and NOS2 are critical regulators of the innate response to L. major.

摘要

2型一氧化氮合酶（NOS2）是细胞内微生物（包括硕大利什曼原虫）感染依赖Th1的愈合所必需的。在此，我们证明了NOS2在对硕大利什曼原虫的天然免疫反应中的表达并确定了其功能。在感染第1天，NOS2的基因缺失或功能失活消除了IFNγ和自然杀伤细胞反应，增加了TGFβ的表达，并导致寄生虫从皮肤和淋巴结扩散至脾脏、肝脏、骨髓和肺部。NOS2的诱导依赖于IFNα/β。IFNα/β的中和模拟了NOS2基因敲除小鼠的表型。因此，IFNα/β和NOS2是对硕大利什曼原虫天然免疫反应的关键调节因子。