ovalbumin and Klebsiella-Infections

The Th17 cytokines interleukin-17A (IL-17A), IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens, including Klebsiella pneumoniae. Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminish ex vivo and in vivo IL-17A protein expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infection, we developed a combined model in which allergic airway inflammation and lung IL-4 and IL-13 expression were induced by ovalbumin sensitization and challenge prior to acute lung infection with K. pneumoniae. We hypothesized that preexisting allergic airway inflammation decreases lung IL-17A expression and airway neutrophil recruitment in response to acute K. pneumoniae infection and thereby increases the lung K. pneumoniae burden. As hypothesized, we found that allergic airway inflammation decreased the number of K. pneumoniae-induced airway neutrophils and lung IL-17A, IL-17F, and IL-22 expression. Despite the marked reduction in postinfection airway neutrophilia and lung expression of Th17 cytokines, allergic airway inflammation significantly decreased the lung K. pneumoniae burden and postinfection mortality. We showed that the decreased lung K. pneumoniae burden was independent of IL-4, IL-5, and IL-17A and partially dependent on IL-13 and STAT6. Additionally, we demonstrated that the decreased lung K. pneumoniae burden associated with allergic airway inflammation was both neutrophil and CCL8 dependent. These findings suggest a novel role for CCL8 in lung antibacterial immunity against K. pneumoniae and suggest new mechanisms of orchestrating lung antibacterial immunity.

Topics: Animals; Chemokine CCL8; Eosinophils; Female; Hypersensitivity; Inflammation; Interleukins; Klebsiella Infections; Klebsiella pneumoniae; Lung; Mice; Mice, Inbred BALB C; Neutrophils; Ovalbumin; Pneumonia, Bacterial

It has been previously observed that lipopolysaccharides can be detoxified by alkylation and yet retain their adjuvant activity. Our present findings confirm these results and show, moreover, that these derivatives did not lose their capacity to protect mice against lethal irradiation and lost only partially their ability to interrupt pregnancy or to induce blast transformation of murine B-lymphocytes. However, in contrast with lipopolysaccharides, these alkylated preparations did not enhance the nonspecific resistance of mice to a bacterial infection. The various bilogical functions of endotoxins can therefore be separated and are not uniformly related to their toxicity.

Topics: Abortion, Spontaneous; Adjuvants, Immunologic; Alkylation; Animals; Endotoxins; Female; Guinea Pigs; Hemagglutination Inhibition Tests; Immunization; Influenza Vaccines; Klebsiella Infections; Lipopolysaccharides; Mice; Mice, Inbred AKR; Mice, Inbred C57BL; Ovalbumin; Pregnancy; Rabbits; Radiation Protection; Serum Albumin, Bovine

Topics: Animals; Bacteria; Blood Proteins; Drug Resistance, Microbial; Escherichia coli; Hydrogen-Ion Concentration; Klebsiella; Klebsiella Infections; Mice; Microbial Sensitivity Tests; Ovalbumin; Pneumococcal Infections; Proline; Staphylococcal Infections; Staphylococcus; Streptococcal Infections; Tetracycline; Tetracyclines