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Comparison of Pulmonary Inflammatory and Antioxidant Responses to Intranasal Live and Heat-Killed Streptococcus pneumoniae in Mice

Abstract

Inflammatory and antioxidant responses, in male C57Bl6J mice, to single intranasal inoculations with live or heat-killed Streptococcus pneumoniae were studied in order to tease out differences in responses. Heat-killed bacteria elicited weak lung neutrophil infiltration and raised concentrations (peak 6–8 h), in serum or lung tissue, of CXCL1 and 2, tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and granulocyte-macrophage-colony stimulating factor, with later increases in CCL2 and IL-1β. Live bacteria induced profound pulmonary neutrophil infiltration and acute chemokine/cytokine elevations. After 72–96 h, live S. pneumoniae induced a delayed rise in chemokines CXCL2 and CCL2, preceded by increases in TNFα, IL-1β, and IL-6 and mononuclear infiltration of lungs. With both live and heat-killed bacteria, alveolar epithelial type II cells and alveolar macrophages were the main sources of TNFα and IL-1β. Only live bacteria caused an acute decrease in lung glutathione peroxidase, an increase in superoxide dismutase, and a sustained increase in serum amyloid protein A. Acute innate immune responses to live and heat-killed S. pneumoniae are similar. In response to live bacteria, inflammation is greater, accompanied by changes in antioxidant enzymes and has an additional, later mononuclear component.

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ACKNOWLEDGEMENTS

We thank Željko Javorščak, Vedran Vrban, Slavica Skender, Ksenija Štajcer and Marija Škalic for excellent technical assistance.

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Correspondence to Miroslava Dominis-Kramari.

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Dominis-Kramari, M., Bosnar, M., Kelneri, Ž. et al. Comparison of Pulmonary Inflammatory and Antioxidant Responses to Intranasal Live and Heat-Killed Streptococcus pneumoniae in Mice. Inflammation 34, 471–486 (2011). https://doi.org/10.1007/s10753-010-9255-7

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  • DOI: https://doi.org/10.1007/s10753-010-9255-7

KEY WORDS

  • S. pneumoniae infection
  • murine lung inflammation
  • pro-inflammatory cytokines
  • antioxidant enzymes