title: Allergic airway inflammation decreases lung bacterial burden following acute Klebsiella pneumoniae infection in a neutrophil- and CCL8-dependent manner.
abstract: 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.
authors: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors: Daniel E
authors: DE
authors: Dulek
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors: Dawn C
authors: DC
authors: Newcomb
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors: Kasia
authors: K
authors: Goleniewska
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors: Jaqueline
authors: J
authors: Cephus
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors: Weisong
authors: W
authors: Zhou
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors: Sara
authors: S
authors: Reiss
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors: Shinji
authors: S
authors: Toki
authors: Department of Biostatistics and Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors: Fei
authors: F
authors: Ye
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors: Rinat
authors: R
authors: Zaynagetdinov
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors: Taylor P
authors: TP
authors: Sherrill
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors: Timothy S
authors: TS
authors: Blackwell
authors: Department of Pediatrics, Emory University, and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
authors: Martin L
authors: ML
authors: Moore
authors: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors: Kelli L
authors: KL
authors: Boyd
authors: Department of Pediatrics, University of Pittsburgh, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: Jay K
authors: JK
authors: Kolls
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA stokes.peebles@vanderbilt.edu.
authors: R Stokes
authors: RS
authors: Peebles
mesh_terms: D000818:Animals; D054412:Chemokine CCL8 / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology / Q000382:microbiology; D005260:Female; D006967:Hypersensitivity / Q000276:immunology* / Q000382:microbiology; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology; D007378:Interleukins / Q000276:immunology; D007710:Klebsiella Infections / Q000276:immunology* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D010047:Ovalbumin / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology
chemical_list: C515454:Ccl8 protein, mouse; D054412:Chemokine CCL8; D007378:Interleukins; D010047:Ovalbumin