Jing Zhang1,2, Ming Guo2, Yan Rao2, Yong Wang2, Qiaoyang Xian2, Qian Yu2, Zhixiang Huang2, Xin Wang2, Rong Bao2, Junqiu Yue3, Zhijiao Tang2, Ke Zhuang2, Li Zhou2, Zhuoya Li1. 1. Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. 2. Animal Biosafety Level III Laboratory at the Center for Animal Experiment, Wuhan University School of Medicine, Wuhan 430072, China. 3. Department of Pathology, Hubei Cancer Hospital, Wuhan 430070, China.
Abstract
BACKGROUND: Nearly one-third of the population worldwide is estimated to have latent tuberculosis infection (LTBI), which represents a vast reservoir for a constant source of tuberculosis (TB) transmission. It has been suggested that cynomolgus macaques are less susceptible to Mycobacterium tuberculosis (M.tb) infection than rhesus macaques, we examined M.tb infection of Chinese cynomolgus macaques. METHODS: Eight Chinese cynomolgus macaques were infected with M.tb Erdman strain with a small [25 colony forming unit (CFU)] or large dose (500 CFU) via bronchoscopy. The infected animals were monitored for symptoms and examined by chest X-ray, computed tomography (CT), tuberculin skin test (TST), and enzyme-linked immunospot (ELISPOT). RESULTS: Based on TST conversion and the specific immune responses to M.tb antigens, all animals were successfully infected. Half of the animals developed active infection and died within 15 months postinfection. The other four animals were grouped with latent M.tb infection because of positive TST but few clinical signs and pathological changes of TB during the course of this study. Interestingly, a challenge with a large dose of M.tb also induced latent infection. Similar to the changes that occur with human TB patients, the animals with active infection exhibited weight loss, cough and typical TB pathological changes, including caseous granulomas, cavities, consolidation, lipid pneumonia, pleural effusion, lymphadenopathy and bacterial burden in lungs and other organs. CONCLUSIONS: The low dose of M.tb was sufficient to cause both active and latent M.tb infection in cynomolgus macaques of Chinese origin.
BACKGROUND: Nearly one-third of the population worldwide is estimated to have latent tuberculosis infection (LTBI), which represents a vast reservoir for a constant source of tuberculosis (TB) transmission. It has been suggested that cynomolgus macaques are less susceptible to Mycobacterium tuberculosis (M.tb) infection than rhesus macaques, we examined M.tb infection of Chinese cynomolgus macaques. METHODS: Eight Chinese cynomolgus macaques were infected with M.tb Erdman strain with a small [25 colony forming unit (CFU)] or large dose (500 CFU) via bronchoscopy. The infected animals were monitored for symptoms and examined by chest X-ray, computed tomography (CT), tuberculin skin test (TST), and enzyme-linked immunospot (ELISPOT). RESULTS: Based on TST conversion and the specific immune responses to M.tb antigens, all animals were successfully infected. Half of the animals developed active infection and died within 15 months postinfection. The other four animals were grouped with latent M.tb infection because of positive TST but few clinical signs and pathological changes of TB during the course of this study. Interestingly, a challenge with a large dose of M.tb also induced latent infection. Similar to the changes that occur with human TB patients, the animals with active infection exhibited weight loss, cough and typical TB pathological changes, including caseous granulomas, cavities, consolidation, lipid pneumonia, pleural effusion, lymphadenopathy and bacterial burden in lungs and other organs. CONCLUSIONS: The low dose of M.tb was sufficient to cause both active and latent M.tb infection in cynomolgus macaques of Chinese origin.
Entities:
Keywords:
Chinese cynomolgus macaques; Erdman strain; Mycobacterium tuberculosis (M.tb); active infection; latent tuberculosis; non-human primate (NHP)
Authors: Crystal Y Chen; Shuyu Yao; Dan Huang; Huiyong Wei; Helene Sicard; Gucheng Zeng; Hassan Jomaa; Michelle H Larsen; William R Jacobs; Richard Wang; Norman Letvin; Yun Shen; Liyou Qiu; Ling Shen; Zheng W Chen Journal: PLoS Pathog Date: 2013-08-15 Impact factor: 6.823