The success of Streptococcus pneumoniae (the pneumococcus) as a pulmonary pathogen is related to its restriction of innate immune responses by respiratory epithelial cells. The mechanisms used to overcome this restriction are incompletely elucidated. Pulmonary chemokine expression involves complex cellular and molecular networks, involving the pulmonary epithelium, but the specific cellular interactions and the cytokines that control them are incompletely defined. We show that serotype 2 or 4 pneumococci induce only modest levels of CXCL8 expression from epithelial cell lines, even in the absence of polysaccharide capsule. In contrast, co-culture of A549 cells with the macrophage-like THP-1 cell-line, differentiated with Vitamin D, or monocyte-derived macrophages, enhanced CXCL8 release. Supernatants from the THP-1 cell-line prime A549 cells to release CXCL8 at levels similar to co-cultures. IL-1Ra inhibits CXCL8 release from co-cultures and reduces the activity of macrophage-conditioned media, but inhibition of TNFα had only a minimal effect on CXCL8 release. Release of IL-1β but not TNFα was upregulated in co-cultures. IL-1 type 1 receptor knockout C57BL/6 and BALB/c mice confirmed the importance of IL-1 signaling in CXC chemokine expression and neutrophil recruitment in vivo. In fulminant disease increased IL-1 signaling resulted in increased neutrophils in the airway and more invasive disease. These results demonstrate that IL-1 is an important component of the cellular network involving macrophages and epithelial cells, which facilitates CXC chemokine expression and aids neutrophil recruitment during pneumococcal pneumonia. They also highlight a potential clinical role for anti-IL-1 treatment to limit excessive neutrophilic inflammation in the lung.
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|Titolo:||IL-1β regulates CXCL8 release and influences disease outcome in response to Streptococcus pneumoniae, defining intracellular cooperation between pulmonary epithelial cells and macrophages.|
|Citazione:||H. M., M., K. A., G., R., G., I., G., M. J., H., Iannelli, F., et al. (2012). IL-1β regulates CXCL8 release and influences disease outcome in response to Streptococcus pneumoniae, defining intracellular cooperation between pulmonary epithelial cells and macrophages. INFECTION AND IMMUNITY, 80(3), 1140-1149.|
|Appare nelle tipologie:||1.1 Articolo in rivista|
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