MODULATION OF INNATE IMMUNE DEFENSES BY MYCOBACTERIUM TUBERCULOSIS

结核分枝杆菌对先天免疫防御的调节

• 批准号: 8357560
• 负责人: Jyothi Rengarajan
• 金额: $ 4.12万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357560
• 关键词: Biochemical; Cessation of life; Environment; Funding; Grant; Host Defense; Hydrolase; Immune; Immune response; Infection; Lipoproteins; Molecular; Mycobacterium tuberculosis; Names; National Center for Research Resources; Natural Immunity; Pathogenesis; Pathway interactions; Primates; Principal Investigator; Proteins; Public Health; Receptor Signaling; Research; Research Infrastructure; Resistance; Resources; Serine Hydrolase; Source; Stress; Toll-like receptors; Tuberculosis; United States National Institutes of Health; Virulence; cell envelope; cost; in vivo; macrophage; microbicide; mutant; novel vaccines; response; tuberculosis drugs

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Tuberculosis (TB) remains a major threat to global public health and infection with Mycobacterium tuberculosis (Mtb) is estimated to result in over 2 million deaths annually. In order to develop new vaccines and drugs for TB, we need to understand how Mtb evades innate immunity and survives in hostile immune environments. A central feature of Mtb pathogenesis is its ability to grow within macrophages, modulate their activities and interfere with microbicidal functions. We have identified a cell envelope-localized lipoprotein encoding a serine hydrolase, Rv2224c, which is critical for Mtb virulence in vivo, survival in macrophages and resistance to cell envelope-directed stresses. We have named this protein Hip1 (Hydrolase important for pathogenesis 1). We demonstrate that Hip1 suppresses innate immune responses; hip1 mutants induce enhanced proinflammatory responses downstream of Toll-like receptor (TLR)-signaling in macrophages. We hypothesize that Hip1 modifies cell envelope or secreted substrates to modulate innate immunity and host defense. The focus of this project is to understand how Hip1 suppresses host innate immune pathways and determine the molecular and biochemical mechanisms for Hip1 function.

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