Cited by 129Immune Response and InflammationImmune responses and vaccinationsAntimicrobial Peptides and Activities

Stimulated Innate Resistance of Lung Epithelium Protects Mice Broadly against Bacteria and Fungi

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Evans, Scott E., Scott, Brenton L., Clement, Cecilia G., Larson, Derek T., Kontoyiannis, Dimitrios, Lewis, Russell E., LaSala, P. Rocco, Pawlik, Jennifer +8 more·2010·American Journal of Respiratory Cell and Molecular Biology

Abstract

Pneumonia is a serious problem worldwide. We recently demonstrated that innate defense mechanisms of the lung are highly inducible against pneumococcal pneumonia. To determine the breadth of protection conferred by stimulation of lung mucosal innate immunity, and to identify cells and signaling pathways activated by this treatment, mice were treated with an aerosolized bacterial lysate, then challenged with lethal doses of bacterial and fungal pathogens. Mice were highly protected against a broad array of Gram-positive, Gram-negative, and class A bioterror bacterial pathogens, and the fungal pathogen, Aspergillus fumigatus. Protection was associated with rapid pathogen killing within the lungs, and this effect was recapitulated in vitro using a respiratory epithelial cell line. Gene expression analysis of lung tissue showed marked activation of NF-κB, type I and II IFN, and antifungal Card9-Bcl10-Malt1 pathways. Cytokines were the most strongly induced genes, but the inflammatory cytokines TNF and IL-6 were not required for protection. Lung-expressed antimicrobial peptides were also highly up-regulated. Taken together, stimulated innate resistance appears to occur through the activation of multiple host defense signaling pathways in lung epithelial cells, inducing rapid pathogen killing, and conferring broad protection against virulent bacterial and fungal pathogens. Augmentation of innate antimicrobial defenses of the lungs might have therapeutic value for protection of patients with neutropenia or impaired adaptive immunity against opportunistic pneumonia, and for defense of immunocompetent subjects against a bioterror threat or epidemic respiratory infection.

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  • Interferon types I and III, produced by ECs upon fungal recognition, could induce the recruitment of neutrophils.

    “Interferon (IFN) types I and III, produced by ECs upon fungal recognition, could induce the recruitment of neutrophils (230, 231).”

    From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [230]

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  1. [23]Comer JE, Noffsinger DM, McHenry DJ, Weisbaum DM, Chatuev BM, Chopra AK, Peterson JW. Evaluation of the protective effects of quinacrine against Bacillus anthracis Ames. J Toxicol Environ Health A 2006;69:1083–1095. [DOI] [PubMed] [Google Scholar]

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Authors
Evans, S. E., Scott, B. L., Clement, C. G., Larson, D. T., Kontoyiannis, D., Lewis, R. E., LaSala, P. R., Pawlik, J., Peterson, J. W., Chopra, A. K., Klimpel, G., Bowden, G., Höök, M., Xu, Y., Tuvim, M. J., & Dickey, B. F.
Affiliations
  • Texas A&M Health Science Center (US)
  • The University of Texas MD Anderson Cancer Center (US)
  • Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas
  • The University of Texas Medical Branch at Galveston (US)
  • Center for Lung Inflammation and Infection, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas
Venue
American Journal of Respiratory Cell and Molecular Biology
Published
2010-01-01
Volume
42
Issue
1
Pages
40-50
ISSN
  • 1044-1549 (ISSN-L)
  • 1535-4989
OpenAlex
W2106845589
Cited by
129
References
51
Citations by year
2026: 5 · 2025: 1 · 2024: 3 · 2023: 7 · 2022: 5 · 2021: 7 · 2020: 22 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 3 · 2015: 10 · 2014: 6 · 2013: 11 · 2012: 12
FWCI
5.31
Type
journal article
Language
en
Open access
Locations
  • American Journal of Respiratory Cell and Molecular Biology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Health and Human Services
  • National Institutes of Health (n01ai15437-16-0-3, CA- 016672)
  • National Heart, Lung, and Blood Institute (HL072984, R01HL072984)
  • National Cancer Institute (P30CA16672, CA 105352, U01CA105352, P30CA016672)
  • National Institute of Allergy and Infectious Diseases (AI 30065, AI064389, AI15437, R01AI064389, U01AI082226, AI 5385802)
  • National Center for Research Resources (KL2-RR-02419)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
  • Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
Keywords
lung epithelium, innate immunity, pneumococcal pneumonia, bacterial extracts, Aspergillus fumigatus, fungal pneumonia, NF-κB, interferon, antimicrobial peptides, cytokines, TNF-α, interleukin-6, airway epithelial cells, opportunistic pneumonia, neutropenia
MeSH terms
Aerosols, Animals, Bacterial Infections, Epithelial Cells, Female, Gene Expression Regulation, Immunity, Innate, Inflammation, Lung, Male, Mice, Inbred C57BL, Mycoses, Pneumonia, Time Factors, Mice

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