生物谷报道：被结核杆菌（Mycobacterium tuberculosis）感染的10个人中仅有约1人在临床上真会患上结核病。压力、营养不良、同时伴随感染以及年龄等都影响易感性，身体在遗传上的抵抗力也影响易感性。现在，研究人员在小鼠身上识别出一种调节对结核病先天免疫力的基因。该基因名叫“细胞内病原体抗性基因”（Ipr1），它在巨噬细胞中的表达不仅限制结核杆菌的表达，而且还限制李斯特菌（Listeria monocytogenes）的表达。人体中与Ipr1蛋白最接近的同源蛋白（41%相同）是核体蛋白SP110，所以SP110基因是验证与结核病易感性之间联系的一个候选基因。
该文发表在： Nature 434, 767 - 772 (07 April 2005); doi:10.1038/nature03419
Ipr1 gene mediates innate immunity to tuberculosis
HUI PAN1,*, BO-SHIUN YAN1,*, MAURICIO ROJAS1,3,*, YURIY V. SHEBZUKHOV1,†, HONGWEI ZHOU2, LESTER KOBZIK2, DARREN E. HIGGINS4, MARK J. DALY5, BARRY R. BLOOM1 & IGOR KRAMNIK1
1 Department of Immunology and Infectious Diseases, Harvard School of Public Health, 667 Huntington Avenue, Boston, Massachusetts 02115, USA
2 Physiology Program, Department of Environmental Health, Harvard School of Public Health, 667 Huntington Avenue, Boston, Massachusetts 02115, USA
3 Grupo de Inmunología Celular e Inmunogenética, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
4 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
5 Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
* These authors contributed equally to this work
† Present address: Department of Molecular Immunology, A. N. Belozersky Institute of Physical and Chemical Biology, Moscow State University, Vorobjovy Gory, Moscow, 119899, Russia
Correspondence and requests for materials should be addressed to I.K. (ikramnik@hsph.harvard.edu).
The Ipr1 sequence has been deposited in GenBank under accession number AY845948.
An estimated eight million people are infected each year with the pathogen Mycobacterium tuberculosis, and more than two million die annually. Yet only about 10% of those infected develop tuberculosis. Genetic variation within host populations is known to be significant in humans and animals, but the nature of genetic control of host resistance to tuberculosis remains poorly understood. Previously we mapped a new genetic locus on mouse chromosome 1, designated sst1 (for supersusceptibility to tuberculosis 1). Here we show that this locus mediates innate immunity in sst1 congenic mouse strains and identify a candidate gene, Intracellular pathogen resistance 1 (Ipr1), within the sst1 locus. The Ipr1 gene is upregulated in the sst1 resistant macrophages after activation and infection, but it is not expressed in the sst1 susceptible macrophages. Expression of the Ipr1 transgene in the sst1 susceptible macrophages limits the multiplication not only of M. tuberculosis but also of Listeria monocytogenes and switches a cell death pathway of the infected macrophages from necrosis to apoptosis. Our data indicate that the Ipr1 gene product might have a previously undocumented function in integrating signals generated by intracellular pathogens with mechanisms controlling innate immunity, cell death and pathogenesis.
