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 journalArticle

128 Citations (Scopus)

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
StatePublished - 1997

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Cryptococcosis
Interleukin-12
Interferons
Monoclonal Antibodies
Lung
Cytokines
Cryptococcus neoformans
T-cells
Macrophages
Nitric Oxide Synthase Type II
Antibodies
Eosinophilia
Infection
Inbred C57BL Mouse
Cellular Immunity
Lymph Nodes
T-Lymphocytes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Pulmonary and Respiratory Medicine

Cite this

IL-12 and IFN-γ are required for initiating the protective Th1 response to pulmonary cryptococcosis in resistant C.B-17 Mice. / Hoag, Kathleen A.; Lipscomb, Mary F.; Izzo, Angelo A.; Street, Nancy E.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 17, No. 6, 1997, p. 733-739.

Research output: Contribution to journalArticle

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