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Interleukin-1 regulates CXCL8 release and influences disease outcome in response to streptococcus pneumoniae, defining intercellular cooperation between pulmonary epithelial cells and macrophages

Marriott, H. M., Gascoyne, K. A., Gowda, R., Geary, I., Nicklin, M. J. H., Iannelli, F., Pozzi, G., Mitchell, T. J., Whyte, M. K. B., Sabroe, I. and Dockrell, D. H. (2012) Interleukin-1 regulates CXCL8 release and influences disease outcome in response to streptococcus pneumoniae, defining intercellular cooperation between pulmonary epithelial cells and macrophages. Infection and Immunity, 80 (3). pp. 1140-1149. ISSN 0019-9567

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Abstract

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 a polysaccharide capsule. In contrast, coculture 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 cocultures. Interleukin-1Ra (IL-1Ra) inhibits CXCL8 release from cocultures and reduces the activity of macrophage-conditioned media, but inhibition of tumor necrosis factor alpha (TNF-alpha) had only a minimal effect on CXCL8 release. Release of IL-1 beta but not TNF-alpha was upregulated in cocultures. 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.

Item Type: Article
Copyright, Publisher and Additional Information: © 2012 American Society of Microbiology. This is an author produced version of a paper subsequently published in Infection and Immunity. Uploaded in accordance with the publisher's self-archiving policy.
Keywords: Impaired Host-Defense; Tumor-Necrosis-Factor; Pneumococcal Pneumonia; Inflammatory Responses; Neutrophil Recruitment; Human-Monocytes; Deficient Mice; THP-1 Cells; I Receptor; Lung
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield) > Department of Infection & Immunity
Depositing User: Miss Anthea Tucker
Date Deposited: 21 Mar 2012 09:43
Last Modified: 08 Feb 2013 17:37
Published Version: http://dx.doi.org/10.1128/IAI.05697-11
Status: Published
Publisher: American Society for Microbiology
Refereed: Yes
Identification Number: 10.1128/IAI.05697-11
URI: http://eprints.whiterose.ac.uk/id/eprint/43771

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