| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Pathology and Kaplan Comprehensive Cancer Center,
Cell Biology, and
Pathology and Heidelberger Division of Immunology, New York University School of Medicine, New York, NY 10016;
§
Children’s Hospital Research Foundation and Ohio State University Comprehensive Cancer Center, Columbus, OH 43205; and
¶
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029
IFNs protect from virus infection by inducing an antiviral state
and by modulating the immune response. Using mice deficient in multiple
aspects of IFN signaling, we found that type I and type II IFN play
distinct although complementing roles in the resolution of influenza
viral disease. Both types of IFN influenced the profile of cytokines
produced by T lymphocytes, with a significant bias toward Th2
differentiation occurring in the absence of responsiveness to either
IFN. However, although a Th1 bias produced through inhibition of Th2
differentiation by IFN-
was not required to resolve infection, loss
of type I IFN responsiveness led to exacerbated disease pathology
characterized by granulocytic pulmonary inflammatory infiltrates.
Responsiveness to type I IFN did not influence the generation of
virus-specific cytotoxic lymphocytes or the rate of viral clearance,
but induction of IL-10 and IL-15 in infected lungs through a type I
IFN-dependent pathway correlated with a protective response to virus.
Combined loss of both IFN pathways led to a severely polarized
proinflammatory immune response and exacerbated disease. These results
reveal an unexpected role for type I IFN in coordinating the host
response to viral infection and controlling inflammation in the absence
of a direct effect on virus replication.
This article has been cited by other articles:
|
|
 |
|
  I. Najjar, P. O. Schischmanoff, F. Baran-Marszak, P.-A. Deglesne, I. Youlyouz-Marfak, M. Pampin, J. Feuillard, G. W. Bornkamm, M. K. Chelbi-Alix, and R. Fagard Novel function of STAT1{beta} in B cells: induction of cell death by a mechanism different from that of STAT1{alpha} J. Leukoc. Biol., December 1, 2008; 84(6): 1604 - 1612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kubota, M. Matsuoka, T.-H. Chang, P. Tailor, T. Sasaki, M. Tashiro, A. Kato, and K. Ozato Virus Infection Triggers SUMOylation of IRF3 and IRF7, Leading to the Negative Regulation of Type I Interferon Gene Expression J. Biol. Chem., September 12, 2008; 283(37): 25660 - 25670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. T. Mars, A.-S. Gautron, J. Novak, L. Beaudoin, J. Diana, R. S. Liblau, and A. Lehuen Invariant NKT Cells Regulate Experimental Autoimmune Encephalomyelitis and Infiltrate the Central Nervous System in a CD1d-Independent Manner J. Immunol., August 15, 2008; 181(4): 2321 - 2329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-L. Baron, D. Gauchat, R. La Motte-Mohs, N. Kettaf, A. Abdallah, T. Michiels, J.-C. Zuniga-Pflucker, and R.-P. Sekaly TLR Ligand-Induced Type I IFNs Affect Thymopoiesis J. Immunol., June 1, 2008; 180(11): 7134 - 7146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Diao, S. Li, Y. Tian, M. Zhang, L.-G. Xu, Y. Zhang, R.-P. Wang, D. Chen, Z. Zhai, B. Zhong, et al. Negative regulation of MDA5- but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase PNAS, July 10, 2007; 104(28): 11706 - 11711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Ho and L. B. Ivashkiv Role of STAT3 in Type I Interferon Responses: NEGATIVE REGULATION OF STAT1-DEPENDENT INFLAMMATORY GENE ACTIVATION J. Biol. Chem., May 19, 2006; 281(20): 14111 - 14118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. S. Coro, W. L. W. Chang, and N. Baumgarth Type I IFN Receptor Signals Directly Stimulate Local B Cells Early following Influenza Virus Infection J. Immunol., April 1, 2006; 176(7): 4343 - 4351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zha, K.-J. Han, L.-G. Xu, W. He, Q. Zhou, D. Chen, Z. Zhai, and H.-B. Shu The Ret Finger Protein Inhibits Signaling Mediated by the Noncanonical and Canonical I{kappa}B Kinase Family Members J. Immunol., January 15, 2006; 176(2): 1072 - 1080. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhang, K. Takami, M. S. Lo, G. Huang, Q. Yu, W. T. Roswit, and M. J. Holtzman Modification of the Stat1 SH2 Domain Broadly Improves Interferon Efficacy in Proportion to p300/CREB-binding Protein Coactivator Recruitment J. Biol. Chem., October 7, 2005; 280(40): 34306 - 34315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Abel, D. M. Rocke, B. Chohan, L. Fritts, and C. J. Miller Temporal and Anatomic Relationship between Virus Replication and Cytokine Gene Expression after Vaginal Simian Immunodeficiency Virus Infection J. Virol., October 1, 2005; 79(19): 12164 - 12172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Holtzman, J. W. Tyner, E. Y. Kim, M. S. Lo, A. C. Patel, L. P. Shornick, E. Agapov, and Y. Zhang Acute and Chronic Airway Responses to Viral Infection: Implications for Asthma and Chronic Obstructive Pulmonary Disease Proceedings of the ATS, August 1, 2005; 2(2): 132 - 140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gimeno, C.-K. Lee, C. Schindler, and D. E. Levy Stat1 and Stat2 but Not Stat3 Arbitrate Contradictory Growth Signals Elicited by Alpha/Beta Interferon in T Lymphocytes Mol. Cell. Biol., July 1, 2005; 25(13): 5456 - 5465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Hu, H. H. Ho, O. Lou, C. Hidaka, and L. B. Ivashkiv Homeostatic Role of Interferons Conferred by Inhibition of IL-1-Mediated Inflammation and Tissue Destruction J. Immunol., July 1, 2005; 175(1): 131 - 138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Johnson, S. E. Mertz, N. Gitiban, S. Hammond, R. LeGallo, R. K. Durbin, and J. E. Durbin Role for Innate IFNs in Determining Respiratory Syncytial Virus Immunopathology J. Immunol., June 1, 2005; 174(11): 7234 - 7241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Prakash, E. Smith, C.-k. Lee, and D. E. Levy Tissue-specific Positive Feedback Requirements for Production of Type I Interferon following Virus Infection J. Biol. Chem., May 13, 2005; 280(19): 18651 - 18657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. N. Meissner, S. Swain, M. Tighe, A. Harmsen, and A. Harmsen Role of Type I IFNs in Pulmonary Complications of Pneumocystis murina Infection J. Immunol., May 1, 2005; 174(9): 5462 - 5471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Dikopoulos, A. Bertoletti, A. Kroger, H. Hauser, R. Schirmbeck, and J. Reimann Type I IFN Negatively Regulates CD8+ T Cell Responses through IL-10-Producing CD4+ T Regulatory 1 Cells J. Immunol., January 1, 2005; 174(1): 99 - 109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ferko, J. Stasakova, J. Romanova, C. Kittel, S. Sereinig, H. Katinger, and A. Egorov Immunogenicity and Protection Efficacy of Replication-Deficient Influenza A Viruses with Altered NS1 Genes J. Virol., December 1, 2004; 78(23): 13037 - 13045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Baskin, A. Garcia-Sastre, T. M. Tumpey, H. Bielefeldt-Ohmann, V. S. Carter, E. Nistal-Villan, and M. G. Katze Integration of Clinical Data, Pathology, and cDNA Microarrays in Influenza Virus-Infected Pigtailed Macaques (Macaca nemestrina) J. Virol., October 1, 2004; 78(19): 10420 - 10432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Anfossi, S. H. Robbins, S. Ugolini, P. Georgel, K. Hoebe, C. Bouneaud, C. Ronet, A. Kaser, C. B. DiCioccio, E. Tomasello, et al. Expansion and Function of CD8+ T Cells Expressing Ly49 Inhibitory Receptors Specific for MHC Class I Molecules J. Immunol., September 15, 2004; 173(6): 3773 - 3782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Auerbuch, D. G. Brockstedt, N. Meyer-Morse, M. O'Riordan, and D. A. Portnoy Mice Lacking the Type I Interferon Receptor Are Resistant to Listeria monocytogenes J. Exp. Med., August 16, 2004; 200(4): 527 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Strengell, I. Julkunen, and S. Matikainen IFN-{alpha} regulates IL-21 and IL-21R expression in human NK and T cells J. Leukoc. Biol., August 1, 2004; 76(2): 416 - 422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Punturieri, R. S. Alviani, T. Polak, P. Copper, J. Sonstein, and J. L. Curtis Specific Engagement of TLR4 or TLR3 Does Not Lead to IFN-{beta}-Mediated Innate Signal Amplification and STAT1 Phosphorylation in Resident Murine Alveolar Macrophages J. Immunol., July 15, 2004; 173(2): 1033 - 1042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Rothfuchs, C. Trumstedt, H. Wigzell, and M. E. Rottenberg Intracellular Bacterial Infection-Induced IFN-{gamma} Is Critically but Not Solely Dependent on Toll-Like Receptor 4-Myeloid Differentiation Factor 88-IFN-{alpha}{beta}-STAT1 Signaling J. Immunol., May 15, 2004; 172(10): 6345 - 6353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nishibori, Y. Tanabe, L. Su, and M. David Impaired Development of CD4+ CD25+ Regulatory T Cells in the Absence of STAT1: Increased Susceptibility to Autoimmune Disease J. Exp. Med., January 5, 2004; 199(1): 25 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Abel, M. J. Alegria-Hartman, K. Rothaeusler, M. Marthas, and C. J. Miller The Relationship between Simian Immunodeficiency Virus RNA Levels and the mRNA Levels of Alpha/Beta Interferons (IFN-{alpha}/{beta}) and IFN-{alpha}/{beta}-Inducible Mx in Lymphoid Tissues of Rhesus Macaques during Acute and Chronic Infection J. Virol., July 17, 2002; 76(16): 8433 - 8445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Durbin, T. R. Johnson, R. K. Durbin, S. E. Mertz, R. A. Morotti, R. S. Peebles, and B. S. Graham The Role of IFN in Respiratory Syncytial Virus Pathogenesis J. Immunol., March 15, 2002; 168(6): 2944 - 2952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J Boyton and P. J Openshaw Pulmonary defences to acute respiratory infection Br. Med. Bull., March 1, 2002; 61(1): 1 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Holtzman, J. D. Morton, L. P. Shornick, J. W. Tyner, M. P. O'Sullivan, A. Antao, M. Lo, M. Castro, and M. J. Walter Immunity, Inflammation, and Remodeling in the Airway Epithelial Barrier: Epithelial-Viral-Allergic Paradigm Physiol Rev, January 1, 2002; 82(1): 19 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ferko, J. Stasakova, S. Sereinig, J. Romanova, D. Katinger, B. Niebler, H. Katinger, and A. Egorov Hyperattenuated Recombinant Influenza A Virus Nonstructural-Protein-Encoding Vectors Induce Human Immunodeficiency Virus Type 1 Nef-Specific Systemic and Mucosal Immune Responses in Mice J. Virol., October 1, 2001; 75(19): 8899 - 8908. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Collins and M. D. Grounds The Role of Tumor Necrosis Factor-alpha (TNF-{alpha}) in Skeletal Muscle Regeneration: Studies in TNF-{alpha}(-/-) and TNF-{alpha}(-/-)/LT-{alpha}(-/-) Mice J. Histochem. Cytochem., August 1, 2001; 49(8): 989 - 1002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Levings, R. Sangregorio, F. Galbiati, S. Squadrone, R. de Waal Malefyt, and M.-G. Roncarolo IFN-{{alpha}} and IL-10 Induce the Differentiation of Human Type 1 T Regulatory Cells J. Immunol., May 1, 2001; 166(9): 5530 - 5539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wang and D. E. Lewis CD86 expression correlates with amounts of HIV produced by macrophages in vitro J. Leukoc. Biol., March 1, 2001; 69(3): 405 - 413. [Abstract] [Full Text]
|
|
|
|
|
|
H. Ito, J. Kurtz, J. Shaffer, and M. Sykes CD4 T Cell-Mediated Alloresistance to Fully MHC-Mismatched Allogeneic Bone Marrow Engraftment Is Dependent on CD40-CD40 Ligand Interactions, and Lasting T Cell Tolerance Is Induced by Bone Marrow Transplantation with Initial Blockade of this Pathway J. Immunol., March 1, 2001; 166(5): 2970 - 2981. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-G. Roncarolo, M. K. Levings, and C. Traversari Differentiation of T Regulatory Cells by Immature Dendritic Cells J. Exp. Med., January 16, 2001; 193(2): F5 - F10. [Full Text] [PDF]
|
|
|
|
|
|
C.-K. Lee, D. T. Rao, R. Gertner, R. Gimeno, A. B. Frey, and D. E. Levy Distinct Requirements for IFNs and STAT1 in NK Cell Function J. Immunol., October 1, 2000; 165(7): 3571 - 3577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lefebvre, S. Berrih-Aknin, F. Adrian, P. Moreau, S. Poea, L. Gourand, J. Dausset, E. D. Carosella, and P. Paul A Specific Interferon (IFN)-stimulated Response Element of the Distal HLA-G Promoter Binds IFN-regulatory Factor 1 and Mediates Enhancement of This Nonclassical Class I Gene by IFN-beta J. Biol. Chem., February 23, 2001; 276(9): 6133 - 6139. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
