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Tuberculosis (Edinb). 2014 Jan;94(1):55-64. doi: 10.1016/j.tube.2013.09.004. Epub 2013 Sep 19.

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

Author information

1
Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, CIBERES, Unitat de Tuberculosi Experimental, Crtra. de Can Ruti, Camí de les Escoles, s/n, 08916 Badalona, Barcelona, Catalonia, Spain. Electronic address: elena.marzo.e@gmail.com.
2
Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, CIBERES, Unitat de Tuberculosi Experimental, Crtra. de Can Ruti, Camí de les Escoles, s/n, 08916 Badalona, Barcelona, Catalonia, Spain. Electronic address: cvilaplana@gmail.com.
3
Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Pathology Department, Crtra. de Can Ruti, s/n, 08916 Badalona, Barcelona, Catalonia, Spain. Electronic address: gustavotapiam@hotmail.com.
4
Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, CIBERES, Unitat de Tuberculosi Experimental, Crtra. de Can Ruti, Camí de les Escoles, s/n, 08916 Badalona, Barcelona, Catalonia, Spain. Electronic address: jortxe@gmail.com.
5
Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, CIBERES, Unitat de Tuberculosi Experimental, Crtra. de Can Ruti, Camí de les Escoles, s/n, 08916 Badalona, Barcelona, Catalonia, Spain. Electronic address: neva23_@hotmail.com.
6
Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, CIBERES, Unitat de Tuberculosi Experimental, Crtra. de Can Ruti, Camí de les Escoles, s/n, 08916 Badalona, Barcelona, Catalonia, Spain. Electronic address: pjcardona@igtp.cat.

Abstract

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 × 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 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.

KEYWORDS:

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

PMID:
24291066
DOI:
10.1016/j.tube.2013.09.004
[Indexed for MEDLINE]

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