Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

J. Exp. Med. 205 (2): 323-329

Copyright © 2008 by the Rockefeller University Press.


BRIEF DEFINITIVE REPORT

Sustained desensitization to bacterial Toll-like receptor ligands after resolutionof respiratory influenza infection

Arnaud Didierlaurent1, John Goulding1, Seema Patel1, Robert Snelgrove1, Lionel Low1, Magali Bebien1, Toby Lawrence1, Leonie S. van Rijt2, Bart N. Lambrecht2, Jean-Claude Sirard3, , and Tracy Hussell1

1 Kennedy Institute of Rheumatology, Imperial College London, London W6 8LH, England, UK
2 Department of Pulmonary Medicine, Erasmus Medical Center, 3015 GE Rotterdam, Netherlands
3 INSERM U801, Equipe Avenir d'Immunité Anti-Microbienne des Muqueuses, Institut Pasteur de Lille-Institut de Biologie, 59000 Lille, France

CORRESPONDENCE Tracy Hussell: t.hussell{at}imperial.ac.uk OR Arnaud Didierlaurent: a.didierlaurent{at}imperial.ac.uk

Abstract: The World Health Organization estimates that lower respiratory tract infections (excluding tuberculosis) account for ~35% of all deaths caused by infectious diseases. In many cases, the cause of death may be caused by multiple pathogens, e.g., the life-threatening bacterial pneumonia observed in patients infected with influenza virus. The ability to evolve more efficient immunity on each successive encounter with antigen is the hallmark of the adaptive immune response. However, in the absence of cross-reactive T and B cell epitopes, one lung infection can modify immunity and pathology to the next for extended periods of time. We now report for the first time that this phenomenon is mediated by a sustained desensitization of lung sentinel cells to Toll-like receptor (TLR) ligands; this is an effect that lasts for several months after resolution of influenza or respiratory syncytial virus infection and is associated with reduced chemokine production and NF-{kappa}B activation in alveolar macrophages. Although such desensitization may be beneficial in alleviating overall immunopathology, the reduced neutrophil recruitment correlates with heightened bacterial load during secondary respiratory infection. Our data therefore suggests that post-viral desensitization to TLR signals may be one possible contributor to the common secondary bacterial pneumonia associated with pandemic and seasonal influenza infection.


M. Bebien and T. Lawrence's present address is Institute of Cancer, Centre for Translational Oncology, Bart's and The London School of Medicine and Dentistry, London EC1M 6BQ, UK.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Influenza Infection Suppresses NADPH Oxidase-Dependent Phagocytic Bacterial Clearance and Enhances Susceptibility to Secondary Methicillin-Resistant Staphylococcus aureus Infection.
K. Sun and D. W. Metzger (2014)
J. Immunol. 192, 3301-3307
   Abstract »    Full Text »    PDF »
Influenza A Virus Impairs Control of Mycobacterium tuberculosis Coinfection Through a Type I Interferon Receptor-Dependent Pathway.
P. S. Redford, K. D. Mayer-Barber, F. W. McNab, E. Stavropoulos, A. Wack, A. Sher, and A. O'Garra (2014)
The Journal of Infectious Disease 209, 270-274
   Abstract »    Full Text »    PDF »
The yin and the yang of immunosuppression with inhaled corticosteroids.
I. Sabroe, D. Postma, I. Heijink, and D. H. Dockrell (2013)
Thorax 68, 1085-1087
   Full Text »    PDF »
The amazing innate immune response to influenza A virus infection.
S. Tripathi, M. R. White, and K. L. Hartshorn (2013)
Innate Immunity
   Abstract »    Full Text »    PDF »
Expression of innate immune genes, proteins and microRNAs in lung tissue of pigs infected experimentally with influenza virus (H1N2).
K. Skovgaard, S. Cirera, D. Vasby, A. Podolska, S. O. Breum, R. Durrwald, M. Schlegel, and P. M. Heegaard (2013)
Innate Immunity 19, 531-544
   Abstract »    Full Text »    PDF »
Genome-wide fitness profiling reveals adaptations required by Haemophilus in coinfection with influenza A virus in the murine lung.
S. M. Wong, M. Bernui, H. Shen, and B. J. Akerley (2013)
PNAS 110, 15413-15418
   Abstract »    Full Text »    PDF »
Immune Dysfunction and Bacterial Coinfections following Influenza.
D. W. Metzger and K. Sun (2013)
J. Immunol. 191, 2047-2052
   Abstract »    Full Text »    PDF »
Influenza A Virus Infection Impairs Mycobacteria-Specific T Cell Responses and Mycobacterial Clearance in the Lung during Pulmonary Coinfection.
M. Florido, M. A. Grima, C. M. Gillis, Y. Xia, S. J. Turner, J. A. Triccas, J. Stambas, and W. J. Britton (2013)
J. Immunol. 191, 302-311
   Abstract »    Full Text »    PDF »
Role of Tissue Protection in Lethal Respiratory Viral-Bacterial Coinfection.
A. M. Jamieson, L. Pasman, S. Yu, P. Gamradt, R. J. Homer, T. Decker, and R. Medzhitov (2013)
Science 340, 1230-1234
   Abstract »    Full Text »    PDF »
The Alveolar Microenvironment of Patients Infected with Human Immunodeficiency Virus Does Not Modify Alveolar Macrophage Interactions with Streptococcus pneumoniae.
S. B. Gordon, R. T. Jagoe, E. R. Jarman, J. C. North, A. Pridmore, J. Musaya, N. French, E. E. Zijlstra, M. E. Molyneux, and R. C. Read (2013)
Clin. Vaccine Immunol. 20, 882-891
   Abstract »    Full Text »    PDF »
Invasive Bacterial Infections in Relation to Influenza Outbreaks, 2006-2010.
D. Tasher, M. Stein, E. A. F. Simoes, T. Shohat, M. Bromberg, and E. Somekh (2011)
Clinical Infectious Diseases 53, 1199-1207
   Abstract »    Full Text »    PDF »
Lowering the Threshold of Lung Innate Immune Cell Activation Alters Susceptibility to Secondary Bacterial Superinfection.
J. Goulding, A. Godlee, S. Vekaria, M. Hilty, R. Snelgrove, and T. Hussell (2011)
The Journal of Infectious Disease 204, 1086-1094
   Abstract »    Full Text »    PDF »
Expression and function of toll-like receptors in peripheral blood mononuclear cells of patients with polymyalgia rheumatica and giant cell arteritis.
L. Alvarez Rodriguez, M. Lopez-Hoyos, C. Mata, A. Fontalba, J. Calvo Alen, M. J. Marin, J. L. Fernandez-Luna, J. Aguero Balbin, M. Aranzamendi Zaldunbide, R. Blanco, et al. (2011)
Ann Rheum Dis 70, 1677-1683
   Abstract »    Full Text »    PDF »
Influenza vaccination is associated with reduced severity of community-acquired pneumonia.
A. Tessmer, T. Welte, R. Schmidt-Ott, S. Eberle, G. Barten, N. Suttorp, T. Schaberg, and for the CAPNETZ study group (2011)
Eur. Respir. J. 38, 147-153
   Abstract »    Full Text »    PDF »
Long-term impairment of Streptococcus pneumoniae lung clearance is observed after initial infection with influenza A virus but not human metapneumovirus in mice.
H. P. Ludewick, L. Aerts, M.-E. Hamelin, and G. Boivin (2011)
J. Gen. Virol. 92, 1662-1665
   Abstract »    Full Text »    PDF »
Influenza Virus Primes Mice for Pneumonia From Staphylococcus aureus.
A. R. Iverson, K. L. Boyd, J. L. McAuley, L. R. Plano, M. E. Hart, and J. A. McCullers (2011)
The Journal of Infectious Disease 203, 880-888
   Abstract »    Full Text »    PDF »
Influenza A Inhibits Th17-Mediated Host Defense against Bacterial Pneumonia in Mice.
A. Kudva, E. V. Scheller, K. M. Robinson, C. R. Crowe, S. M. Choi, S. R. Slight, S. A. Khader, P. J. Dubin, R. I. Enelow, J. K. Kolls, et al. (2011)
J. Immunol. 186, 1666-1674
   Abstract »    Full Text »    PDF »
Seasonal FluMist Vaccination Induces Cross-Reactive T Cell Immunity against H1N1 (2009) Influenza and Secondary Bacterial Infections.
K. Sun, J. Ye, D. R. Perez, and D. W. Metzger (2011)
J. Immunol. 186, 987-993
   Abstract »    Full Text »    PDF »
Lactobacillus-Mediated Priming of the Respiratory Mucosa Protects against Lethal Pneumovirus Infection.
S. J. Gabryszewski, O. Bachar, K. D. Dyer, C. M. Percopo, K. E. Killoran, J. B. Domachowske, and H. F. Rosenberg (2011)
J. Immunol. 186, 1151-1161
   Abstract »    Full Text »    PDF »
The Airway Epithelium: Soldier in the Fight against Respiratory Viruses.
M. Vareille, E. Kieninger, M. R. Edwards, and N. Regamey (2011)
Clin. Microbiol. Rev. 24, 210-229
   Abstract »    Full Text »    PDF »
TLR5 Signaling Stimulates the Innate Production of IL-17 and IL-22 by CD3negCD127+ Immune Cells in Spleen and Mucosa.
L. Van Maele, C. Carnoy, D. Cayet, P. Songhet, L. Dumoutier, I. Ferrero, L. Janot, F. Erard, J. Bertout, H. Leger, et al. (2010)
J. Immunol. 185, 1177-1185
   Abstract »    Full Text »    PDF »
Influenza A virus facilitates Streptococcus pneumoniae transmission and disease.
D. A. Diavatopoulos, K. R. Short, J. T. Price, J. J. Wilksch, L. E. Brown, D. E. Briles, R. A. Strugnell, and O. L. Wijburg (2010)
FASEB J 24, 1789-1798
   Abstract »    Full Text »    PDF »
Delivery of Cytokines by Recombinant Virus in Early Life Alters the Immune Response to Adult Lung Infection.
J. A. Harker, D. C. P. Lee, Y. Yamaguchi, B. Wang, A. Bukreyev, P. L. Collins, J. S. Tregoning, and P. J. M. Openshaw (2010)
J. Virol. 84, 5294-5302
   Abstract »    Full Text »    PDF »
Influenza Infection Leads to Increased Susceptibility to Subsequent Bacterial Superinfection by Impairing NK Cell Responses in the Lung.
C.-L. Small, C. R. Shaler, S. McCormick, M. Jeyanathan, D. Damjanovic, E. G. Brown, P. Arck, M. Jordana, C. Kaushic, A. A. Ashkar, et al. (2010)
J. Immunol. 184, 2048-2056
   Abstract »    Full Text »    PDF »
Dysregulated Macrophage-Inflammatory Protein-2 Expression Drives Illness in Bacterial Superinfection of Influenza.
C. C. J. Zavitz, C. M. T. Bauer, G. J. Gaschler, K. M. Fraser, R. M. Strieter, C. M. Hogaboam, and M. R. Stampfli (2010)
J. Immunol. 184, 2001-2013
   Abstract »    Full Text »    PDF »
Respiratory Viral Infections in Infants: Causes, Clinical Symptoms, Virology, and Immunology.
J. S. Tregoning and J. Schwarze (2010)
Clin. Microbiol. Rev. 23, 74-98
   Abstract »    Full Text »    PDF »
Immune dysregulation in severe influenza.
M. L. Heltzer, S. E. Coffin, K. Maurer, A. Bagashev, Z. Zhang, J. S. Orange, and K. E. Sullivan (2009)
J. Leukoc. Biol. 85, 1036-1043
   Abstract »    Full Text »    PDF »
Subversion of Pulmonary Dendritic Cell Function by Paramyxovirus Infections.
A. Guerrero-Plata, D. Kolli, C. Hong, A. Casola, and R. P. Garofalo (2009)
J. Immunol. 182, 3072-3083
   Abstract »    Full Text »    PDF »
Infection with Human Metapneumovirus Predisposes Mice to Severe Pneumococcal Pneumonia.
I. Kukavica-Ibrulj, M.-E. Hamelin, G. A. Prince, C. Gagnon, Y. Bergeron, M. G. Bergeron, and G. Boivin (2009)
J. Virol. 83, 1341-1349
   Abstract »    Full Text »    PDF »
Predominant Role of Bacterial Pneumonia as a Cause of Death in Pandemic Influenza: Implications for Pandemic Influenza Preparedness.
D. M.. Morens, J. K. Taubenberger, and A. S. Fauci (2008)
The Journal of Infectious Disease 198, 962-970
   Abstract »    Full Text »    PDF »
Inchoate CD8+ T Cell Responses in Neonatal Mice Permit Influenza-Induced Persistent Pulmonary Dysfunction.
D. You, M. Ripple, S. Balakrishna, D. Troxclair, D. Sandquist, L. Ding, T. A. Ahlert, and S. A. Cormier (2008)
J. Immunol. 181, 3486-3494
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882