生物谷報道：被結核桿菌（Mycobacterium tuberculosis）感染的10個人中僅有約1人在臨床上真會患上結核病,。壓力,、營養(yǎng)不良,、同時伴隨感染以及年齡等都影響易感性,，身體在遺傳上的抵抗力也影響易感性?，F在，研究人員在小鼠身上識別出一種調節(jié)對結核病先天免疫力的基因,。該基因名叫“細胞內病原體抗性基因”（Ipr1）,，它在巨噬細胞中的表達不僅限制結核桿菌的表達，而且還限制李斯特菌（Listeria monocytogenes）的表達,。人體中與Ipr1蛋白最接近的同源蛋白（41%相同）是核體蛋白SP110,，所以SP110基因是驗證與結核病易感性之間聯系的一個候選基因。
該文發(fā)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. ([email protected]).
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.
