Abstract

Introduction. Streptococcus pneumoniae is the most prevalent cause of community-acquired pneumonia worldwide. Previous data obtained in our laboratory show a major role of the anti-inflammatory cytokine IL-10 in host survival during pneumococcal pneumonia. Specifically, IL-10 production is important to modulate lung inflammation and neutrophil accumulation in the lung tissue. In addition, several reports have described a major ability of neutrophils to produce IL-10 during inflammation. However, whether these cells produce IL-10 in the lung tissue during S. pneumoniae remains unknown. Hypothesis. We hypothesized that neutrophils are major IL-10 producing cells during S. pneumoniae pneumonia and, therefore, are major modulators of the lung immune response. Objectives. 1. To evaluate the ability of neutrophils to produce IL-10 in vivo. 2. To evaluate whether bacterial recognition by these cells is enough to trigger its production. Methodology. To evaluate the ability of neutrophils to produce IL-10 in vivo, IL-10/GFP Vertx mice were intranasally infected with 3x107 CFUs and IL-10 production kinetic by neutrophils was followed by flow cytometry during 24 and 48 hours post-infection (hpi). Next, to evaluate whether S. pneumoniae molecular patterns trigger IL-10 production in neutrophils, bone marrow isolated neutrophils were exposed to heat killed S. pneumoniae for 24 hours and IL-10 was quantified by ELISA in the supernatant. Results. As compared to other innate cells, neutrophils showed to be the major IL-10 producing cells after 24 hpi. Moreover, the direct contact of bone marrow derived neutrophils with S. pneumoniae induced the production of IL-10. Conclusions. In this study we provide strong evidence regarding the ability of neutrophils, but not other immune cells, to produce IL-10 during S. pneumoniae in the lung tissue at early time post infection. Moreover, recognition of S. pneumoniae molecular patterns by neutrophils is enough to trigger the production of IL-10 by these cells. In summary, our data suggest that neutrophils are major modulators of the immune response during S. pneumoniae pneumonia.