Superinfecting mycobacteria home to established granulomas超感染分枝杆菌肉芽肿回家了.ppt

Superinfecting mycobacteria home to established granulomas Christine L. Cosma, Oliver Humbert Lalita Ramakrishnan Presented by Donica Larson May 10, 2005 Background Mycobacterium tuberculosis Gram-positive rod Non-motile Acid Fast positive Causative agent of tuberculosis (TB) Often is in state of clinical latency Bacteria persist undetected for decades before leading to active disease Background Tuberculosis is the most common major infectious disease today, infecting two billion people. 9 million new cases of active disease annually 2 million deaths, mostly in developing countries 90% have asymptomatic latent TB infection (LTBI). 10% lifetime chance that LTBI will progress to active TB disease untreated, kills 50% of victims One of the top three infectious killing diseases in the world HIV/AIDS kills 3 million people each year TB kills 2 million malaria kills 1 million Introduction The bacteria Mycobacterium marinum: causes systemic chronic tuberculosis in ectotherms Salmonella enterica serovar Arizonae: macrophage pathogen of ectotherms The hosts Frog model (Rana pipiens): study of trafficking into granulomas Zebrafish model (Danio rerio): observation of caseating granulomas Neither is demonstrated in mouse model Introduction Infection: initial infection causing granulomas Superinfection: subsequent infection after granulomas are established Granuloma: complex immune structures that comprise differentiated macrophages, lymphocytes other immune cells Caseum: located w/in granulomas, central area of necrosis. Develop in mature lesions Results 1) Protection against M. marinum superinfection in preinfected frogs Do frogs chronically infected w/ M. marinum have partial immunity to superinfections? Pre-infect frogs w/ wt M. marinum for 6 wks (3.3 x 106 CFU) Infect na?ve and pre-infected frogs w/ kanamycin resistant M. marinum Count kanamycin resistant bacteria 2 wks and 8 wks later 1-2 log less burden in pre-infected frogs 2) Myc