The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Stimulated Innate Resistance of Lung Epithelium Protects Mice Broadly against Bacteria and Fungi
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Recognition of microorganisms and activation of the immune response
Medzhitov, R. (2007) · Nature · doi:10.1038/nature06246 · Cited by 2,862
Updating the accounts: global mortality of the 1918–1920 "Spanish" influenza pandemic.
Johnson, N. P. A. S., & Mueller, J. (2002) · Bulletin of the History of Medicine · doi:10.1353/bhm.2002.0022 · Cited by 1,980
Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron
Flo, T. H., Smith, K. D., Sato, S., Rodriguez, D. J., Holmes, M. A., Strong, R. K., Akira, S., & Aderem, A. (2004) · Nature · doi:10.1038/nature03104 · Cited by 1,877
Impaired immune and acute-phase responses in interleukin-6-deficient mice
Kopf, M., Baumann, H., Freer, G., Freudenberg, M., Lamers, M., Kishimoto, T., Zinkernagel, R., Bluethmann, H., & Köhler, G. (1994) · Nature · doi:10.1038/368339a0 · Cited by 1,768 · cited 1×
“Although IL-62/2 mice have an increased baseline susceptibility to bacterial infections relative to wild-type C57BL/6 mice (29), we were still able to induce protection and rapid pathogen killing with NTHi lysate in the mutant mice (Figures 5E and 5F).”
BackgroundIL-22 Increases the Innate Immunity of Tissues
Wolk, K., Kunz, S., Witte, E., Friedrich, M., Asadullah, K., & Sabat, R. (2004) · Immunity · doi:10.1016/j.immuni.2004.07.007 · Cited by 1,406
Cooperation of Toll-like receptor signals in innate immune defence
Trinchieri, G., & Sher, A. (2007) · Nature reviews. Immunology · doi:10.1038/nri2038 · Cited by 1,394
Gene-specific control of inflammation by TLR-induced chromatin modifications
Foster, S. L., Hargreaves, D. C., & Medzhitov, R. (2007) · Nature · doi:10.1038/nature05836 · Cited by 1,344
Toll-Like Receptor Signaling Pathways
Barton, G. M., & Medzhitov, R. M. (2003) · Science · doi:10.1126/science.1085536 · Cited by 1,270
IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia
Aujla, S. J., Chan, Y. R., Zheng, M., Fei, M., Askew, D. J., Pociask, D. A., Reinhart, T. A., McAllister, F. M., Edeal, J., Gaus, K., et al. (2008) · Nature Medicine · doi:10.1038/nm1710 · Cited by 1,219
Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection
Cheng, V. C. C., Lau, S. K. P., Woo, P. C. Y., & Yuen, K. Y. (2007) · Clinical Microbiology Reviews · doi:10.1128/cmr.00023-07 · Cited by 1,192
Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients
Kuderer, N. M., Dale, D. C., Crawford, J., Cosler, L. E., & Lyman, G. H. (2006) · Cancer · doi:10.1002/cncr.21847 · Cited by 1,177
Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity
Groß, O., Gewies, A., Finger, K., Schäfer, M., Sparwasser, T. D., Peschel, C., Förster, I., & Ruland, J. (2006) · Nature · doi:10.1038/nature04926 · Cited by 871
Disentangling Genetic Variation for Resistance and Tolerance to Infectious Diseases in Animals
Råberg, L., Sim, D. G., & Read, A. F. (2007) · Science · doi:10.1126/science.1148526 · Cited by 785
Staphylococcus aureus Panton-Valentine Leukocidin Causes Necrotizing Pneumonia
Labandeira‐Rey, M., Couzon, F., Boisset, S., Brown, E. L., Bes, M., Benito, Y., Barbu, E. M., Sarathy, V. V., Höök, M., Étienne, J., et al. (2007) · Science · doi:10.1126/science.1137165 · Cited by 707
Self-citationInnate immunity in the lung: how epithelial cells fight against respiratory pathogens
Bals, R., & Hiemstra, P. S. (2004) · European Respiratory Journal · doi:10.1183/09031936.03.00098803 · Cited by 589
Iwasaki, A. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141634 · Cited by 555
Recognition of microbial infection by Toll-like receptors
Kopp, E. B., & Medzhitov, R. M. (2003) · Current Opinion in Immunology · doi:10.1016/s0952-7915(03)00080-3 · Cited by 553
File, T. M. (2003) · The Lancet · doi:10.1016/s0140-6736(03)15021-0 · Cited by 497
Berger, T., Togawa, A., Duncan, G. S., Elia, A. J., You-Ten, A., Wakeham, A., Fong, H. E. H., Cheung, C. C., & Mak, T. W. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510847103 · Cited by 460
Stereotyped and specific gene expression programs in human innate immune responses to bacteria
Boldrick, J. C., Alizadeh, A. A., Diehn, M., Dudoit, S., Liu, C. L., Belcher, C. E., Botstein, D., Staudt, L. M., Brown, P. O., & Relman, D. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.231625398 · Cited by 395
Martin, T. R., & Frevert, C. W. (2005) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200508-090js · Cited by 362
Bagchi, A., Herrup, E. A., Warren, H. S., Trigilio, J., Shin, H., Valentine, C., & Hellman, J. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.2.1164 · Cited by 338
Mucin Is Produced by Clara Cells in the Proximal Airways of Antigen-Challenged Mice
Evans, C. M., Williams, O. W., Tuvim, M. J., Nigam, R., Mixides, G., Blackburn, M. R., DeMayo, F. J., Burns, A. R., Smith, C. G., Reynolds, S. D., et al. (2004) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2004-0060oc · Cited by 283
Self-citationInfectious Complications of Chronic Lymphocytic Leukemia
Wadhwa, P. D., & Morrison, V. A. (2006) · Seminars in Oncology · doi:10.1053/j.seminoncol.2005.12.013 · Cited by 276
Williams, T. N., Mwangi, T., Wambua, S., Peto, T., Weatherall, D. J., Gupta, S., Recker, M., Penman, B. S., Uyoga, S. M., Macharia, A., et al. (2005) · Nature Genetics · doi:10.1038/ng1660 · Cited by 246
Wiederhold, N. P., Kontoyiannis, D. P., Chi, J., Prince, R. A., Tam, V. H., & Lewis, R. E. (2004) · The Journal of Infectious Diseases · doi:10.1086/424465 · Cited by 206
Self-citationIs serum amyloid A an endogenous TLR4 agonist?
Sandri, S., Rodriguez, D., Gomes, E., Monteiro, H. P., Russo, M., & Campa, A. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.0407203 · Cited by 188
Vallon, R., Freuler, F., Desta-Tsedu, N., Robeva, A., Dawson, J., Wenner, P., Engelhardt, P., Bös, L., Schnyder, J., Tschopp, C., et al. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.4.2801 · Cited by 164
Bielinska, A. U., Janczak, K. W., Landers, J. J., Makidon, P. E., Sower, L. E., Peterson, J. W., & Baker, J. R. (2007) · Infection and Immunity · doi:10.1128/iai.00070-07 · Cited by 135
Self-citationRisk of bacteraemia and mortality in patients with haematological malignancies
Nørgaard, M., Larsson, H. J., Pedersen, G., Schønheyder, H. C., & Sørensen, H. T. (2006) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2005.01298.x · Cited by 122
Stimulation of Lung Innate Immunity Protects against Lethal Pneumococcal Pneumonia in Mice
Clement, C. G., Evans, S. E., Evans, C. M., Hawke, D. H., Kobayashi, R., Reynolds, P. R., Moghaddam, S. J., Scott, B. L., Melicoff, E., Adachi, R., et al. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200607-1038oc · Cited by 121
Self-citationNosocomial pneumonia: State of the science
Flanders, S. A., Collard, H. R., & Saint, S. K. (2006) · American Journal of Infection Control · doi:10.1016/j.ajic.2005.07.003 · Cited by 115
Evans, S. E., Hahn, P. Y., McCann, F., Kottom, T. J., Vuk-Pavlović, Z., & LIMPER, A. H. (2005) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2004-0300oc · Cited by 112
Self-citationSynthetic Toll-Like Receptor 4 Agonists Stimulate Innate Resistance to Infectious Challenge
Cluff, C. W., Baldridge, J. R., Stöver, A. G., Evans, J. T., Johnson, D. A., Lacy, M. J., Clawson, V. G., Yorgensen, V. M., Johnson, C. L., Livesay, M. T., et al. (2005) · Infection and Immunity · doi:10.1128/iai.73.5.3044-3052.2005 · Cited by 110
Augmented Lung Inflammation Protects against Influenza A Pneumonia
Tuvim, M. J., Evans, S. E., Clement, C. G., Dickey, B. F., & Gilbert, B. E. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004176 · Cited by 109
Self-citationDeng, J. C., Moore, T. A., Newstead, M. W., Zeng, X., Krieg, A. Μ., & Standiford, T. J. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.8.5148 · Cited by 104
Moghaddam, S. J., Clement, C. G., la Garza, M. M. D., Zou, X., Travis, E. L., Young, H. W. J., Evans, C. M., Tuvim, M. J., & Dickey, B. F. (2007) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2007-0366oc · Cited by 99
Self-citationSverdlovsk revisited: Modeling human inhalation anthrax
Wilkening, D. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509551103 · Cited by 88
Overview: cause and prevention in biowarfare and bioterrorism
Hilleman, M. R. (2002) · Vaccine · doi:10.1016/s0264-410x(02)00300-6 · Cited by 80
Christenson, K., Björkman, L. I., Tängemo, C., & Bylund, J. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0507276 · Cited by 79
TLR-4 pathway mediates the inflammatory response but not bacterial elimination inE. colipneumonia
Lee, J. S., Frevert, C. W., Matute‐Bello, G., Wurfel, M. M., Wong, V. A., Lin, S., RUZINSKI, J. T., Mongovin, S., Goodman, R. B., & Martin, T. R. (2005) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00196.2005 · Cited by 64
Peterson, J. W., Comer, J. E., Baze, W. B., Noffsinger, D. M., Wenglikowski, A., Walberg, K. G., Hardcastle, J. M., Peel, J. E., Bush, K., Taormina, J., et al. (2007) · Infection and Immunity · doi:10.1128/iai.00352-07 · Cited by 58
Self-citationBreakdown of Pulmonary Host Defense in the Immunocompromised Host: Cancer Chemotherapy
Joos, L., & Tamm, M. (2005) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200508-097js · Cited by 53
Bissinger, A. L., Einsele, H., Hamprecht, K., Schumacher, U., Kandolf, R., Loeffler, J., Aepinus, C., Bock, C. –., Jahn, G., & Hebart, H. F. (2005) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2005.03.005 · Cited by 33
Thorn, C. F., & Whitehead, A. S. (2002) · Amyloid · doi:10.3109/13506120209114098 · Cited by 32
Vaccines for the prevention of diseases caused by potential bioweapons
Hassani, M., Patel, M. C., & Pirofski, L. (2004) · Clinical Immunology · doi:10.1016/j.clim.2003.09.010 · Cited by 31
Inflammatory response associated with pulmonary complications in non-HIV immunocompromised patients
Agustı́, C. (2004) · Thorax · doi:10.1136/thx.2004.030551 · Cited by 24
Bouzianas, D. G. (2007) · Expert Review of Anti-infective Therapy · doi:10.1586/14787210.5.4.665 · Cited by 24
Responding to a Small-scale Bioterrorist Anthrax Attack
Schmitt, B. P. (2007) · Archives of Internal Medicine · doi:10.1001/archinte.167.7.655 · Cited by 16
Evaluation of the Protective Effects of Quinacrine AgainstBacillus anthracisAmes
Comer, J. E., Noffsinger, D. M., McHenry, D. J., Weisbaum, D. M., Chatuev, B. M., Chopra, A. K., & Peterson, J. W. (2006) · Journal of Toxicology and Environmental Health · doi:10.1080/15287390500360281 · Cited by 12
Self-citationNosocomial pneumonia in immunosuppressed patients1
Agustı́, C., RANO, A., Sibila, O., & Torres, A. (2003) · Infectious Disease Clinics of North America · doi:10.1016/s0891-5520(03)00076-x · Cited by 9
Research works printed but not linked: 2
- Bull Hist Med
- 2004, Clin Immunol, 111, 1
Cited by
Sorted by citations
Aspergillus fumigatus and Aspergillosis in 2019
Latgé, J.-P., & Chamilos, G. (2019) · Clinical Microbiology Reviews · doi:10.1128/cmr.00140-18 · Cited by 1,400
Muc5b is required for airway defence
Roy, M. G., Livraghi-Butrico, A., Fletcher, A. A., McElwee, M. M., Evans, S. E., Boerner, R. M., Alexander, S. N., Bellinghausen, L. K., Song, A. S., Petrova, Y. M., et al. (2014) · Nature · doi:10.1038/nature12807 · Cited by 764
Self-citationModulating immunity as a therapy for bacterial infections
Hancock, R. E. W., Nijnik, A., & Philpott, D. J. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2745 · Cited by 558
Integrative Physiology of Pneumonia
Quinton, L. J., Walkey, A. J., & Mizgerd, J. P. (2018) · Physiological Reviews · doi:10.1152/physrev.00032.2017 · Cited by 330
Desvignes, L., & Ernst, J. (2009) · Immunity · doi:10.1016/j.immuni.2009.10.007 · Cited by 245
Metadata
- 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
- ORCID
- Venue
- American Journal of Respiratory Cell and Molecular Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-01-01
- Volume
- 42
- Issue
- 1
- Pages
- 40-50
- ISSN
- 1044-1549 (ISSN-L)
- 1535-4989
- PMC
- PMC2809220
- 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
- green
- www.ncbi.nlm.nih.gov
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
