IL-12 and IFN- γ Are Required for Initiating the Protective Th1 Response to Pulmonary Cryptococcosis in Resistant C.B-17 Mice

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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 ...

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