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Lung epithelial apoptosis in influenza virus pneumonia: the role of macrophage-expressed TNF-related apoptosis-inducing ligand
Open accessAbstract
Mononuclear phagocytes have been attributed a crucial role in the host defense toward influenza virus (IV), but their contribution to influenza-induced lung failure is incompletely understood. We demonstrate for the first time that lung-recruited "exudate" macrophages significantly contribute to alveolar epithelial cell (AEC) apoptosis by the release of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in a murine model of influenza-induced pneumonia. Using CC-chemokine receptor 2-deficient (CCR2(-/-)) mice characterized by defective inflammatory macrophage recruitment, and blocking anti-CCR2 antibodies, we show that exudate macrophage accumulation in the lungs of influenza-infected mice is associated with pronounced AEC apoptosis and increased lung leakage and mortality. Among several proapoptotic mediators analyzed, TRAIL messenger RNA was found to be markedly up-regulated in alveolar exudate macrophages as compared with peripheral blood monocytes. Moreover, among the different alveolar-recruited leukocyte subsets, TRAIL protein was predominantly expressed on macrophages. Finally, abrogation of TRAIL signaling in exudate macrophages resulted in significantly reduced AEC apoptosis, attenuated lung leakage, and increased survival upon IV infection. Collectively, these findings demonstrate a key role for exudate macrophages in the induction of alveolar leakage and mortality in IV pneumonia. Epithelial cell apoptosis induced by TRAIL-expressing macrophages is identified as a major underlying mechanism.
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“However, the strategies for differentiation of resident macrophage subsets in the airways and lung tissues are insufficient to distinguish AMs from lung interstitial macrophages or inflammatory monocytic cells invading the lung in response to infections.”
From Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections (2013) · cites this paper as [17]
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Cites
Serbina, N. V., & Pamer, E. G. (2006) · Nature Immunology · doi:10.1038/ni1309 · Cited by 1,658
Characterization of the reconstructed 1918 Spanish influenza pandemic virus
Tumpey, T. M., Basler, C. F., Aguilar, P. V., Zeng, H., Solórzano, A., Swayne, D. E., Cox, N. J., Katz, J. M., Taubenberger, J. K., Palese, P., et al. (2005) · Science · doi:10.1126/science.1119392 · Cited by 1,327
Tsou, C.-L., Peters, W., Si, Y., Slaymaker, S., Aslanian, A. M., Weisberg, S. P., Mack, M., & Charo, I. F. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29919 · Cited by 1,152
A Clonogenic Bone Marrow Progenitor Specific for Macrophages and Dendritic Cells
Fogg, D. K., Sibon, C., Miled, C., Jung, S., Aucouturier, P., Littman, D. R., Cumano, A., & Geissmann, F. (2005) · Science · doi:10.1126/science.1117729 · Cited by 1,050
Cheung, C., Poon, L., Lau, A., Luk, W., Lau, Y., Shortridge, K., Gordon, S., Guan, Y., & Peiris, J. (2002) · The Lancet · doi:10.1016/s0140-6736(02)11772-7 · Cited by 889
Avian Influenza A (H5N1) in 10 Patients in Vietnam
Hien, T. T., Liem, N. T., Dung, N. T., Luong, S. T., Mai, P. P., Châu, N. V. V., Suu, P. T., Dong, V. C., Mai, L. T. Q., Thi, N. T., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040419 · Cited by 854
Kuziel, W. A., Morgan, S. J., Dawson, T. C., Griffin, S., Smithies, O., Ley, K. F., & Maeda, N. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.22.12053 · Cited by 707
Cretney, E., Takeda, K., Yagita∥, H., Glaccum, M. B., Peschon, J. J., & Smyth, M. J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.3.1356 · Cited by 615
Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus
Kash, J. C., Tumpey, T. M., Proll, S. C., Carter, V., Perwitasari, O., Thomas, M. J., Basler, C. F., Palese, P., Taubenberger, J. K., García-Sastre, A., et al. (2006) · Nature · doi:10.1038/nature05181 · Cited by 551
Migratory fate and differentiation of blood monocyte subsets
Tacke, F., & Randolph, G. J. (2006) · Immunobiology · doi:10.1016/j.imbio.2006.05.025 · Cited by 528
Tumpey, T. M., García‐Sastre, A., Taubenberger, J. K., Palese, P., Swayne, D. E., Pantin‐Jackwood, M. J., Schultz‐Cherry, S., Solórzano, A., van Rooijen, N., Katz, J. M., et al. (2005) · Journal of Virology · doi:10.1128/jvi.79.23.14933-14944.2005 · Cited by 504
Akaike, T., Noguchi, Y., Ijiri, S., Setoguchi, K., Suga, M., Zheng, Y., Dietzschold, B., & Maeda, H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.6.2448 · Cited by 490
Monocyte-mediated Tumoricidal Activity via the Tumor Necrosis Factor–related Cytokine, TRAIL
Griffith, T. S., Wiley, S. R., Kubin, M. Z., Sedger, L. M., Maliszewski, C. R., & Fanger, N. A. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.8.1343 · Cited by 477
Expression and Characterization of the Chemokine Receptors CCR2 and CCR5 in Mice
Mack, M., Cihak, J., Simonis, C., Luckow, B., Proudfoot, A. E. I., Plachý, J., Brühl, H., Frink, M., Anders, H., Vielhauer, V., et al. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.7.4697 · Cited by 459
Lin, K. L., Suzuki, Y. A., Nakano, H., Ramsburg, E. A., & Gunn, M. D. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.4.2562 · Cited by 453
Dawson, T. C., Beck, M. A., Kuziel, W. A., Henderson, F. W., & Maeda, N. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65068-7 · Cited by 379
Role of Host Cytokine Responses in the Pathogenesis of Avian H5N1 Influenza Viruses in Mice
Szretter, K. J., Gangappa, S., Lu, X., Smith, C. S., Shieh, W., Zaki, S. R., Sambhara, S. R., Tumpey, T. M., & Katz, J. M. (2006) · Journal of Virology · doi:10.1128/jvi.02336-06 · Cited by 373
Fas/FasL-dependent Apoptosis of Alveolar Cells after Lipopolysaccharide-induced Lung Injury in Mice
KITAMURA, Y., Hashimoto, S., Mizuta, N., Kobayashi, A., Kooguchi, K., Fujiwara, I., & Nakajima, H. (2001) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.163.3.2003065 · Cited by 294
Recruitment of Gr-1+ monocytes is essential for control of acute toxoplasmosis
Robben, P. M., LaRegina, M. C., Kuziel, W. A., & Sibley, L. D. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050054 · Cited by 277
Virus or TLR Agonists Induce TRAIL-Mediated Cytotoxic Activity of Plasmacytoid Dendritic Cells
Chaperot, L., Blum, A., Manches, O., Lui, G., Angel, J., Molens, J., & Plumas, J. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.1.248 · Cited by 256
Wurzer, W. J., Ehrhardt, C., Pleschka, S., Berberich‐Siebelt, F., Wolff, T., Walczak, H., Planz, O., & Ludwig, S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403258200 · Cited by 240
Apoptosis and Epithelial Injury in the Lungs
Martin, T. R., Hagimoto, N., Nakamura, M., & Matute-Bello, G. (2005) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200504-031ac · Cited by 225
Herold, S., von Wulffen, W., Steinmueller, M., Pleschka, S., Kuziel, W. A., Mack, M., Srivastava, M., Seeger, W., Maus, U. A., & Lohmeyer, J. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.3.1817 · Cited by 216
The role of apoptosis in acute lung injury
Martin, T. R., Nakamura, M., & Matute‐Bello, G. (2003) · Critical Care Medicine · doi:10.1097/01.ccm.0000057841.33876.b1 · Cited by 202
Maus, U. A., Waelsch, K., Kuziel, W. A., Delbeck, T., Mack, M., Blackwell, T. S., Christman, J. W., Schlöndorff, D., Seeger, W., & Lohmeyer, J. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.6.3273 · Cited by 202
The Role of CC Chemokine Receptor 2 in Alveolar Monocyte and Neutrophil Immigration in Intact Mice
Maus, U. A., von Grote, K., Kuziel, W. A., Mack, M., Miller, E. J., Cihak, J., Stangassinger, M., Maus, R., Schlöndorff, D., Seeger, W., et al. (2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.2112012 · Cited by 196
Liu, S., Yu, Y., Zhang, M., Wang, W., & Cao, X. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.9.5407 · Cited by 165
Hokeness, K. L., Kuziel, W. A., Biron, C. A., & Salazar‐Mather, T. P. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.3.1549 · Cited by 158
Fas-induced Pulmonary Apoptosis and Inflammation during Indirect Acute Lung Injury
Perl, M., Chung, C., Perl, U., Lomas‐Neira, J., Paepe, M. E. D., Cioffi, W. G., & Ayala, A. (2007) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200611-1743oc · Cited by 153
Lee, D. C. W., Cheung, C. Y., Law, A. H. Y., Mok, C. K. P., Peiris, M. J. S., & Lau, A. S. Y. (2005) · Journal of Virology · doi:10.1128/jvi.79.16.10147-10154.2005 · Cited by 146
Maus, U. A., Herold, S., Muth, H., Maus, R., Ermert, L., Ermert, M., Weißmann, N., Rosseau, S., Seeger, W., Grimminger, F., et al. (2001) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.2001.280.1.l58 · Cited by 138
Acute Respiratory Distress Syndrome Induced by Avian Influenza A (H5N1) Virus in Mice
Xu, T., Qiao, J., Zhao, L., Wang, G., He, G., Li, K., Tian, Y., Gao, M., Wang, J., Wang, H., et al. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200511-1751oc · Cited by 134
Peters, W., Cyster, J. G., Mack, M., Schlöndorff, D., Wolf, A. J., Ernst, J. D., & Charo, I. F. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.12.7647 · Cited by 120
Targeting of Gr‐1+,CCR2+ monocytes in collagen‐induced arthritis
Brühl, H., Cihak, J., Plachý, J., Kunz‐Schughart, L. A., Niedermeier, M., Denzel, A., Gomez, M. R., Talke, Y., Luckow, B., Stangassinger, M., et al. (2007) · Arthritis & Rheumatism · doi:10.1002/art.22854 · Cited by 120
DR5 Knockout Mice Are Compromised in Radiation-Induced Apoptosis
Finnberg, N. K., Gruber, J. J., Fei, P., Rudolph, D., Bric, A., Kim, S., Burns, T. F., Ajuha, H., Page, R., Wu, G. S., et al. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.5.2000-2013.2005 · Cited by 114
Death and survival: viral regulation of TNF signaling pathways
Benedict, C. A., Banks, T. A., & Ware, C. F. (2003) · Current Opinion in Immunology · doi:10.1016/s0952-7915(02)00018-3 · Cited by 112
The potential role of BAX and BCL-2 expression in diffuse alveolar damage.
Guinee, D. G., Brambilla, E. M., Fleming, M. V., Hayashi, T., Rahn, M., Koss, M., Ferrans, V. J., & Travis, W. D. (1997) · PubMed Central · Cited by 105
Ishikawa, E., Nakazawa, M., Yoshinari, M., & Minami, M. (2005) · Journal of Virology · doi:10.1128/jvi.79.12.7658-7663.2005 · Cited by 103
Winter, C., Taut, K., Srivastava, M., Länger, F. P., Mack, M., Briles, D. E., Paton, J. C., Maus, R., Welte, T., Gunn, M. D., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.9.5828 · Cited by 99
Zhou, J., Law, H., Cheung, C. Y., Ng, I. H. Y., Peiris, M. J. S., & Lau, Y. (2006) · The Journal of Infectious Diseases · doi:10.1086/500954 · Cited by 79
Macrophage Turnover Kinetics in the Lungs of Mice Infected with S treptococcus pneumoniae
Taut, K., Winter, C., Briles, D. E., Paton, J. C., Christman, J. W., Maus, R., Baumann, R., Welte, T., & Maus, U. A. (2007) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2007-0132oc · Cited by 74
Morty, R. E., Eickelberg, O., & Seeger, W. (2007) · Intensive Care Medicine · doi:10.1007/s00134-007-0662-7 · Cited by 62
The critically ill avian influenza A (H5N1) patient*
Arabi, Y. M., Gomersall, C. D., Ahmed, Q. A. A., Boynton, B. R., & Memish, Z. A. (2007) · Critical Care Medicine · doi:10.1097/01.ccm.0000262940.34596.4b · Cited by 52
von Wulffen, W., Steinmüller, M., Herold, S., Marsh, L. M., Bulau, P., Seeger, W., Welte, T., Lohmeyer, J., & Maus, U. A. (2007) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200608-1068oc · Cited by 38
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Research works printed but not linked: 3
- 2007, Am. J. Respir. Cell Mol. Biol., 38, 105
- 1997, Am. J. Pathol., 151, 999
- 2006, Nat. Immunol., 7, 311
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Hussell, T., & Bell, T. J. (2014) · Nature Reviews Immunology · doi:10.1038/nri3600 · Cited by 1,377
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Metadata
- Authors
- Herold, S., Steinmueller, M., von Wulffen, W., Cakarova, L., Pinto, R., Pleschka, S., Mack, M., Kuziel, W. A., Corazza, N., Brunner, T., Seeger, W., & Lohmeyer, J.
- Affiliations
- Justus-Liebig-Universität Gießen (DE)
- 1University of Giessen Lung Center, Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine and Infectious Diseases,
- University of Regensburg (DE)
- 4PDL BioPharma Inc., Redwood City, CA 94063
- University of Bern (CH)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2008-12-08
- Volume
- 205
- Issue
- 13
- Pages
- 3065-3077
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2605231
- OpenAlex
- W2105053798
- Cited by
- 376
- References
- 44
- Citations by year
- 2026: 3 · 2025: 19 · 2024: 16 · 2023: 17 · 2022: 26 · 2021: 32 · 2020: 32 · 2019: 16 · 2018: 21 · 2017: 21 · 2016: 23 · 2015: 20 · 2014: 21 · 2013: 21 · 2012: 22
- FWCI
- 15.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- KOPS (University of Konstanz) (submittedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- influenza virus pneumonia, alveolar epithelial cell apoptosis, TRAIL, tumor necrosis factor-related apoptosis-inducing ligand, CCR2, macrophage recruitment, respiratory failure, host defense
- MeSH terms
- Animals, Bronchoalveolar Lavage Fluid, Chimera, Humans, Influenza, Human, Leukocytes, Mononuclear, Lung, Macrophages, Mice, Inbred C57BL, Orthomyxoviridae, Phagocytes, Pneumonia, Apoptosis, Mice, Knockout, Respiratory Mucosa, Apoptosis Regulatory Proteins, Mice, TNF-Related Apoptosis-Inducing Ligand, Receptors, CCR2
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