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

Olga Gil, Evelyn Guirado, Sergi Gordillo, Jorge Díaz, Gustavo Tapia, Cristina Vilaplana, Aurelio Ariza, Vicenç Ausina, Pere Joan Cardona

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29 Citations (Scopus)

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 α/β T receptor, TNF R1, IL-12, IFN-γ, 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 γ/δ 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-γ, 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. © 2006 Elsevier SAS. All rights reserved.
Original languageEnglish
Pages (from-to)628-636
JournalMicrobes and Infection
Volume8
Issue number3
DOIs
Publication statusPublished - 1 Mar 2006

Keywords

  • Cord factor
  • Intragranulomatous necrosis
  • Koch phenomenon
  • LPS
  • Mice
  • Mycobacterium avium complex
  • Mycobacterium tuberculosis
  • Shwartzman reaction
  • Tolerance

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