Allergic Airway Inflammation Decreases Lung Bacterial Burden following Acute Klebsiella pneumoniae Infection in a Neutrophil- and CCL8-Dependent Manner

• Type of Material: Article
• Authors: Daniel E. Dulek, Vanderbilt University; Dawn C. Newcomb, Vanderbilt University; Kasia Goleniewska, Vanderbilt University; Jaqueline Cephus, Vanderbilt University; Weisong Zhou, Vanderbilt University; Sara Reiss, Vanderbilt University; Shinji Toki, Vanderbilt University; Fei Ye, Vanderbilt University; Rinat Zaynagetdinov, Vanderbilt University; Taylor P. Sherrill, Vanderbilt University; Timothy S. Blackwell, Vanderbilt University; Martin Moore, Emory University; Kelli L. Boyd, Vanderbilt University; Jay K. Kolls, University of Pittsburgh; R. Stokes Peebles, Vanderbilt University
• Language: English
• Date: 2014-09-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2014, American Society for Microbiology. All Rights Reserved.
• Final Published Version (URL): http://dx.doi.org/10.1128/IAI.00035-14
• Title of Journal or Parent Work: Infection and Immunity
• ISSN: 0019-9567
• Volume: 82
• Issue: 9
• Start Page: 3723
• End Page: 3739
• Grant/Funding Information: This work was supported by NIH grants U19AI095227, R01AI111820, and R01HL090664 and U.S. Department of Veterans Affairs grant I01BX000624 to R.S.P. D.E.D. was supported by grants T32HD060554 and T32HL094296.
• Keywords: BLOOD-STREAM INFECTIONS; UNITED-STATES; Life Sciences & Biomedicine; TH17 CELLS; PROTEIN-1-ALPHA CCL3; INNATE IMMUNITY; T-CELLS; Infectious Diseases; Immunology; Science & Technology; ANTIBACTERIAL HOST-DEFENSE; INVASIVE PNEUMOCOCCAL DISEASE; MURINE MODEL; CRITICAL MEDIATOR
• Research Categories: Biology, Biostatistics; Health Sciences, Immunology; Biology, Microbiology

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.