Damaging role of neutrophilic infiltration in a mouse model of progressive tuberculosis

Elena Marzo, Cristina Vilaplana, Gustavo Tapia, Jorge Diaz, Vanessa Garcia, Pere Joan Cardona

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59 Citations (Scopus)

Abstract

Summary 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 × 104 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 anti-inflammatory drugs and C3H/HeN animals presented lower levels of pro-inflammatory mediators such as TNF-α, 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. © 2013 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)55-64
JournalTuberculosis
Volume94
Issue number1
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • Active tuberculosis
  • C3HeB/FeJ mice
  • Experimental murine model of tuberculosis
  • Kramnik mouse model
  • Liquefaction
  • Neutrophils

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