Mouse model of pulmonary cavitary tuberculosis and expression of matrix metalloproteinase-9

作者: Alvaro A. Ordonez , Rokeya Tasneen , Supriya Pokkali , Ziyue Xu , Paul J. Converse

DOI: 10.1242/DMM.025643

关键词:

摘要: Cavitation is a key pathological feature of human tuberculosis (TB), and well-recognized risk factor for transmission infection, relapse after treatment the emergence drug resistance. Despite intense interest in mechanisms underlying cavitation its negative impact on outcomes, there has been limited study this phenomenon, owing large part to limitations existing animal models. Although does not occur conventional mouse strains infection with Mycobacterium tuberculosis, cavitary lung lesions have occasionally observed C3HeB/FeJ mice. However, date, no demonstration that can be produced consistently enough support mice as new useful model TB. We utilized serial computed tomography (CT) imaging detect pulmonary aerosol M. tuberculosis. Post-mortem analyses were performed characterize localize matrix metalloproteinases (MMPs) previously implicated TB situ. A total 47-61% infected developed cavities during primary disease or non-curative treatments. Key features TB, including simultaneous presence multiple pathologies, noted tissues. Optical demonstrated increased MMP activity MMP-9 was significantly expressed lesions. Tissue could abrogated by specific inhibitors. In situ, three-dimensional 22.06% CD11b+ signal colocalized MMP-9. represent reliable, economical tractable similarities This should provide an excellent tool better understand pathogenesis effects

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