title: Damaging role of neutrophilic infiltration in a mouse model of progressive tuberculosis.
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.
authors.affiliation: 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.
authors.forename: Elena
authors.initials: E
authors.lastname: Marzo
authors.affiliation: 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.
authors.forename: Cristina
authors.initials: C
authors.lastname: Vilaplana
authors.affiliation: 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.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Tapia
authors.affiliation: 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.
authors.forename: Jorge
authors.initials: J
authors.lastname: Diaz
authors.affiliation: 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.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Garcia
authors.affiliation: 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.
authors.forename: Pere-Joan
authors.initials: PJ
authors.lastname: Cardona
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000032:analysis; D054365:Chemokine CXCL5 / Q000032:analysis; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006099:Granuloma / Q000473:pathology; D007111:Immunity, Cellular / Q000187:drug effects; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D051379:Mice; D008809:Mice, Inbred C3H; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000473:pathology*; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D054365:Chemokine CXCL5; C094739:Cxcl5 protein, mouse; D020381:Interleukin-17; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
keywords: Active tuberculosis; C3HeB/FeJ mice; Experimental murine model of tuberculosis; Kramnik mouse model; Liquefaction; Neutrophils