Journal
TUBERCULOSIS
Volume 94, Issue 1, Pages 55-64Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.tube.2013.09.004
Keywords
Experimental murine model of tuberculosis; Active tuberculosis; C3HeB/FeJ mice; Kramnik mouse model; Neutrophils; Liquefaction
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Funding
- Spanish Government through the CIBER CRP-TB
- FIS [PI11/0172]
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Tuberculosis was studied using an experimental model based on the C3HeB/FeJ mouse strain, which mimics the liquefaction of caseous necrosis occurring during active disease in immunocompetent adults. Mice were intravenously infected with 2 x 10(4) Colony Forming Units of Mycobacterium tuberculosis and their histopathology, immune response, bacillary load, and survival were evaluated. The effects of the administration of drugs with anti-inflammatory activity were examined, and the C3H/HeN mouse strain was also included for comparative purposes. Massive intra-alveolar neutrophilic infiltration led to rapid granuloma growth and coalescence of lesions into superlesions. A central necrotic area appeared showing progressive cellular destruction, the alveoli cell walls being initially conserved (caseous necrosis) but finally destroyed (liquefactive necrosis). Increasing levels of pro-inflammatory mediators were detected in lungs. C3HeB/FeJ treated with antiinflammatory drugs and C3H/HeN animals presented lower levels of pro-inflammatory mediators such as TNF-alpha, IL-17, IL-6 and CXCL5, a lower bacillary load, better histopathology, and increased survival compared with untreated C3HeB/FeJ. The observation of massive neutrophilic infiltration suggests that inflammation may be a key factor in progression towards active tuberculosis. On the basis of our findings, we consider that the C3HeB/FeJ mouse model would be useful for evaluating new therapeutic strategies against human tuberculosis. (C) 2013 Elsevier Ltd. All rights reserved.
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