Importance of tumor necrosis factor-α (TNF-α) in the immune response to pulmonary cryptococcus neoformans (Cne) in mice

A. A. Izzo, K. Hoag, N. Street, M. F. Lipscomb

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Abstract

In a murine pulmonary Cne infection model, anti-TNF-α monoclonal antibodies (mAb), prevented resolution of the lung infection and the ability to adoptively transfer DTH from Cne infected to naive mice. Using this model we showed that resistant C.B-17 mice, capable of resolving a pulmonary Cne infection, mount a Th1 response as evidenced by increased IFN-γ and little IL-4 and IL-5 secretion by cultured lung and lung associated lymph node (LALN) cells. Susceptible C57BL/6 (B6) mice fail to efficiently clear a Cne lung infection and secrete significantly lower levels of IFN-γ and elevated levels of IL-5. We also found that alveolar macrophages (AM) from infected C.B-17 mice produced TNF-α when cultured in vitro, while AM from B6 mice did not. To investigate the role of TNF-α in the development of a Th1 response, C.B-17 mice were treated with anti-TNF-α mAb at days -1 and +1 of infection. Lung and LALN cells from these and control IgG treated mice were examined in vitro for cytokine production after Con A stimulation. Numbers and types of cells recruited to the lung during infection were examined. Cne-infected C.B-17 mice, when treated with anti-TNF-α mAb failed to resolve a pulmonary infection and produced a cytokine pattern in the lungs and LALN's that was indicative of a Th2 response (increased levels of IL-4 and IL-5). Furthermore, although both groups recruited equal numbers of cells into their lungs, the anti-TNF-α treated mice recruited increased numbers of eosinophils. These results clearly show that in C.B-17 mice TNF-α is important in initiating a Th1 response to pulmonary Cne infection.

Original languageEnglish (US)
Pages (from-to)A1060
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

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ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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