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.

Trivalent pneumococcal protein recombinant vaccine protects against lethal Streptococcus pneumoniae pneumonia and correlates with phagocytosis by neutrophils during early pathogenesis

“…Neutrophils can infiltrate into lung at an early stage of lung Spn infection [40,41]. In this study, we found that lung bacterial clearance correlated with higher level of phagocytosis by neutrophils at an early stage in pathogenesis after a potential lethal challenge of Spn by the physiologically relevant intranasal route.…”

Components of Streptococcus pneumoniae Suppress Allergic Airways Disease and NKT Cells by Inducing Regulatory T Cells

“…Significant differences for the entire doseresponse curves between saline-sensitized (Saline) and OVA-sensitized (OVA) controls are shown as ## p , 0.01 and between OVA-sensitized and component-treated OVA-sensitized mice as *p , 0.05 and ** p , 0.01. upon treatment with pneumolysoid or ethanol-killed S. pneumoniae, others have detected such responses. Pneumolysoid B (PdB, otherwise known as F433), which is the same as the Ply used in our study, has residual cytotoxic activity and induces CD4 T cell proliferation and the release of low levels of IFN-g and TNF-a (27) Others have detected cytokine release from murine macrophages stimulated with ethanol-killed S. pneumoniae (28), and heat-killed S. pneumoniae elicited weak neutrophilic airway inflammation and cytokine responses mainly from macrophages (29). These studies indicate that pneumolysin derivatives that completely lack cytotoxic and proinflammatory activities should be used in human studies.…”

Dietary Supplementation with Lactobacilli Improves Emergency Granulopoiesis in Protein-Malnourished Mice and Enhances Respiratory Innate Immune Response

“…It was observed a small and transient peak of GM-CSF in lung of immunocompetent mice after pneumococcal infection which occurred during the early phase of neutrophil infiltration [29]. Although several cytokines can modulate neutrophil production, G-CSF and GM-CSF are the primary regulators of steady-state and emergency granulopoiesis.…”