Intragranulomatous necrosis in pulmonary granulomas is not related to resistance against Mycobacterium tuberculosis infection in experimental murine models induced by aerosol.
Intragranulomatous necrosis is a primary feature in the natural history of human tuberculosis (TB). Unfortunately, this phenomenon is not usually seen in the experimental TB murine model. Artificial induction of this necrosis in pulmonary granulomas (INPG) may be achieved through aerosol inoculation of lipopolysaccharide (LPS) 3 weeks after Mycobacterium tuberculosis infection. At week 9 post-infection, the centre of primary granulomas became larger, showing eosinophilic necrosis. Interestingly, INPG induction was related to mice strains C57BL/6 and 129/Sv, but not to BALB/c and DBA/2. Furthermore, the same pattern was obtained with the induction of infection using a clinical M. tuberculosis strain (UTE 0335R) that naturally induces INPG. In all the mice strains tested, the study of pulmonary mRNA expression revealed a tendency to increase or to maintain the expression of RANTES, interferon-gamma, tumour necrosis factor and iNOS, in both LPS- and UTE 0335R-induced INPG, thus suggesting that this response must be necessary but not sufficient for inducing INPG. Our work supports that INPG induction is a local phenomenon unrelated to the resistant (C57BL/6 and BALB/c) or susceptible (129/Sv and DBA/2) background of mice strains against M. tuberculosis infection.
Guirado
Evelyn
E
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.
Gordillo
Sergi
S
Gil
Olga
O
Díaz
Jorge
J
Tapia
Gustavo
G
Vilaplana
Cristina
C
Ausina
Vicenç
V
Cardona
Pere-Joan
PJ
D000336:Aerosols; D000818:Animals; D018946:Chemokine CCL5 / Q000032:analysis; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000473:pathology; D005260:Female; D015769:Granuloma, Respiratory Tract / Q000382:microbiology / Q000473:pathology*; D006239:Haplotypes; D007371:Interferon-gamma / Q000032:analysis; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008171:Lung Diseases / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009336:Necrosis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D014376:Tuberculosis / Q000382:microbiology / Q000473:pathology*; D014397:Tuberculosis, Pulmonary / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000336:Aerosols; D018946:Chemokine CCL5; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II