Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia

The contribution of neutrophils to lethal sensitivity and cytokine balance governing T1 and T2 host responses was assessed in a murine model of Legion ella pneumophila pneumonia, Neutrophil depletion by administration of granu locyte-specific mAb RB6-8C5 at 1 day before infection rendered mice - 100-f old more susceptible to lethal pneumonia induced by L, pneumophila. However , this treatment did not alter early bacterial clearance, despite a substan tial decrease in neutrophil influx at this time point. Cytokine profiles in the lungs of control mice demonstrated strong T1 responses, characterized by an increase of IFN-gamma and IL-12, In contrast, neutrophil-depleted mic e exhibited significantly lower levels of IFN-gamma and IL-12, and elevatio n of T2 cytokines, IL-4 and IL-10, Immunohistochemistry of bronchoalveolar lavage cells demonstrated the presence of IL-12 in neutrophils, but not alv eolar macrophages, Moreover, IL-12 was detected in lavage cell lysates by E LISA, which was paralleled to neutrophil number. However, intratracheal adm inistration of recombinant murine IL-12 did not restore resistance, whereas reconstitution of IFN-gamma drastically improved bacterial clearance and s urvival in neutrophil-depleted mice. Taken together, these data demonstrate d that neutrophils play crucial roles in primary L, pneumophila infection, not via direct killing but more immunomodulatory effects. Our results sugge st that the early recruitment of neutrophils may contribute to T1 polarizat ion in a murine model of L. pneumophila pneumonia.