Comparison of Pulmonary Inflammatory and Antioxidant Responses to Intranasal Live and Heat-Killed Streptococcus pneumoni
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Comparison of Pulmonary Inflammatory and Antioxidant Responses to Intranasal Live and Heat-Killed Streptococcus pneumoniae in Mice Miroslava Dominis-Kramarić,1,2 Martina Bosnar,1 Željko Kelnerić,1 Ines Glojnarić,1 Snježana Čužić,1 Michael J. Parnham,1 and Vesna Eraković Haber1
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. KEY WORDS: S. pneumoniae infection; murine lung inflammation; pro-inflammatory cytokines; antioxidant enzymes.
clear distinction between direct bacterial and subsequent immunologic responses in experimental studies will therefore help to determine specific targets for improved therapy of CAP. Bergeron and colleagues have performed the most extensive studies on the murine model of S. pneumoniae induced pneumonia (by single inoculation), using both immunocompetent and immunocompromised animals, in order to identify predictive biomarkers of likely outcome [5–7]. They have described five phases of the host response to infection and focused on cellular trafficking, as well as on various inflammatory markers, including tumor necrosis factor alpha (TNFα), interleukin-1 (IL-1), IL-6, leukotriene B4 (LTB4), nitric oxide (NO), and malonaldehyde (MDA) in bronchoalveolar lavage fluid (BAL), lung homogenates, and serum [5]. During the first 4-h period after infection, these authors observed an increase in TNFα, IL-6, and NO in BAL; of TNFα, IL-6, and IL-1 in lung homogenate; and IL-6 in
INTRODUCTION Community acquired pneumonia (CAP), most frequently induced by Streptococcus pneumoniae, is a significant cause of mortality in humans despite the existence of efficacious antibiotics [1–3]. The reason for this gap between therapeutic expectation and practical experience most probably lies in the nature and extent of the immunologic response to the infection, which ca
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