IL-12 and IFN-γ are required for initiating the protective Th1 response to pulmonary cryptococcosis in resistant C.B-17 Mice

Kathleen A. Hoag, Mary F. Lipscomb, Angelo A. Izzo, Nancy E. Street

Research output: Contribution to journalArticlepeer-review

129 Scopus citations

Abstract

A murine model was used to assess the role of cytokines in initiating protective T-cell-mediated immunity in the lung. A pulmonary infection was initiated by intratracheal inoculation of Cryptococcus neoformans (Cne). Previously, we had established that Cne lung clearance was mouse-strain-specific: C.B-17 mice were resistant and developed a Th1-like response, whereas C57BL/6 mice were susceptible and did not develop a Th1 response. In the present study we showed that monoclonal anti-interferon-γ (IFN-γ) and anti-interleukin-12 (IL-12) antibody administration prior to infection of resistant C.B-17 mice inhibited lung clearance of Cne. Cytokine profiles of lung and lung-associated lymph nodes (LALN) from monoclonal antibody (mAb)-treated C.B-17 mice were switched from Th1-like to Th2-like, and mAb-treated C.B-17 mice exhibited lung eosinophilia, which was absent in control C.B-17 mice. Additionally, C.B-17 mice treated with anti-IFN-γ and anti-IL-12 mAb demonstrated a significantly lower percentage of lung macrophages expressing inducible nitric oxide synthase (iNOS) than did control mice. These studies clearly demonstrate that both IFN-γ and IL-12 are required for initiation of a Th1 response in resistant C.B-17 mice.

Original languageEnglish (US)
Pages (from-to)733-739
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume17
Issue number6
DOIs
StatePublished - Jan 1 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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