title: Intragranulomatous necrosis in lungs of mice infected by aerosol with Mycobacterium tuberculosis is related to bacterial load rather than to any one cytokine or T cell type.
abstract: Low dose aerosol infection of C57BL/6 mice with a clinical strain of Mycobacterium tuberculosis (UTE 0335 R) induced intragranulomatous necrosis in pulmonary granulomas (INPG) at week 9 postinfection. Infection of different knockout (KO) mouse strains with UTE 0335 R induced INPG in all strains and established two histopathological patterns. The first pattern was seen in SCID mice and in mice with deleted alpha/beta T receptor, TNF R1, IL-12, IFN-gamma, or iNOS genes, and showed a massive INPG with a high granulomatous infiltration of the lung, a large and homogeneous eosinophilic necrosis full of acid-fast bacilli, with marked karyorrhexis, coarse basophilic necrosis, and surrounded by patches delimited by partially conserved alveolar septum full of PMNs. The second pattern was seen in mice with deleted IL-1 R1, IL-6, IL-10, CD4, CD8 or gamma/delta T cell receptor genes, and showed more discrete lesions with predominant homogeneous eosinophilic necrosis with few bacilli and surrounded by a well-defined lymphocyte-based ring. Local expression of IFN-gamma, iNOS, TNF and RANTES showed no significant differences between these mouse strains generating a discrete INPG. Mouse strains showing a massive INPG showed higher, lower or equal expression values compared to the control strain. In conclusion, the severity of the INPG pattern correlated with pulmonary CFU counts, irrespective of the genetic absence or the infection-induced levels of cytokine mediators.
authors.affiliation: Unitat de Tuberculosi Experimental, Department of Microbiology, Fundació Institut per a la Investigació en Ciències de la Salut Germans Trias i Pujol and Universitat Autònoma de Barcelona, Catalonia, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Gil
authors.forename: Evelyn
authors.initials: E
authors.lastname: Guirado
authors.forename: Sergi
authors.initials: S
authors.lastname: Gordillo
authors.forename: Jorge
authors.initials: J
authors.lastname: Díaz
authors.forename: Gustavo
authors.initials: G
authors.lastname: Tapia
authors.forename: Cristina
authors.initials: C
authors.lastname: Vilaplana
authors.forename: Aurelio
authors.initials: A
authors.lastname: Ariza
authors.forename: Vicenç
authors.initials: V
authors.lastname: Ausina
authors.forename: Pere-Joan
authors.initials: PJ
authors.lastname: Cardona
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D008168:Lung / Q000382:microbiology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009336:Necrosis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D014397:Tuberculosis, Pulmonary / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger