I read the paper entitled “Chronic alcohol consumption increases the severity of murine influenza virus infections” by Meyerholz and colleagues (1). The authors demonstrated an important fact that chronic alcoholic consumption increased influenza severity. To answer why this happened, they focused on a decrease in CD8+ T cells, which was considered to be main reason. The result is consistent with the finding that mice lacking CD8+ T cells have increased viral replication and morbidity after infection with influenza PR8 virus (2). However, host response to influenza virus infection is a complicated system that includes an intact and functional cascade of changes; each element may play an important role. CD8+ T cells are probably one of many elements of host immune responses decreased by ethanol. These responses include innate immunity (cytokine and IFN production, macrophage function, dendritic cells, and NK cell function) and adaptive immunity (cytotoxic T lymphocyte activity as well as influenza-specific IgM and IgG antibodies). It has been shown that defects in IFN-α and -β lead to increased morbidity and mortality in mice (3, 4). Influenza virus produces NP protein to inhibit IFN-β, indicating its importance in the immune response against influenza (5). NK cells and macrophages are very early responders and have also been demonstrated to be critical for host survival of the infection (6). Plasmacytoid dendritic cells present virus Ag to CD8+ T cells through MHCI and is also important for host immune responses (7). CD4+ and CD8+ T cells and B cells act together; each one alone is not sufficient to overcome virus. For example, CD4+ T cells can help B cells to produce Ab (8). Both activation of CD4+ and CD8 need their costimulators, OX40 and 4-1BBL, respectively (9). Thus, they work in combination to fight virus and single element defect could be compensated by others. It is also important to examine other immune responses, especially Ab production, which appears as early as day 7; they are critical for control of influenza as published recently (10). Indeed, other studies showed that ethanol can inhibit TNF (11, 12), NK cells (13), and IFNγ (14). It also decreases IL-12 and increases IL-10 to cause immune suppression (15).
- Copyright © 2008 by The American Association of Immunologists
References
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Meyerholz, D. K., M. Edsen-Moore, J. McGill, R. A. Coleman, R. T. Cook, K. L. Legge. 2008. Chronic alcohol consumption increases the severity of murine influenza virus infections. J. Immunol. 181: 641-648.
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Bender, B. S., T. Croghan, L. Zhang, P. A. Small, Jr. 1992. Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge. J. Exp. Med. 175: 1143-1145.
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Haller, O., H. Arnheiter, I. Gresser, J. Lindenmann. 1979. Genetically determined, interferon-dependent resistance to influenza virus in mice. J. Exp. Med. 149: 601-612.
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Kopf, M., B. Abel, A. Gallimore, M. Carroll, M. F. Bachmann. 2002. Complement component C3 promotes T-cell priming and lung migration to control acute influenza virus infection. Nat. Med. 8: 373-378.
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Haller, O., G. Kochs, F. Weber. 2006. The interferon response circuit: induction and suppression by pathogenic viruses. Virology 344: 119-130.
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Tsuru, S., H. Fujisawa, M. Taniguchi, Y. Zinnaka, K. Nomoto. 1987. Mechanism of protection during the early phase of a generalized viral infection. II. Contribution of polymorphonuclear leukocytes to protection against intravenous infection with influenza virus. J. Gen. Virol. 68: 419-424.
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Di Pucchio, T., B. Chatterjee, A. Smed-Sorensen, S. Clayton, A. Palazzo, M. Montes, Y. Xue, I. Mellman, J. Banchereau, J. E. Connolly. 2008. Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I. Nat. Immunol. 9: 551-557.
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Doherty, P. C., D. J. Topham, R. A. Tripp, R. D. Cardin, J. W. Brooks, P. G. Stevenson. 1997. Effector CD4+ and CD8+ T-cell mechanisms in the control of respiratory virus infections. Immunol. Rev. 159: 105-117.
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Bertram, E. M., W. Dawicki, T. H. Watts. 2004. Role of T cell costimulation in anti-viral immunity. Semin. Immunol. 16: 185-196.
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Wrammert, J., K. Smith, J. Miller, W. A. Langley, K. Kokko, C. Larsen, N. Y. Zheng, I. Mays, L. Garman, C. Helms, et al 2008. Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature 453: 667-671.
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Omidvari, K., R. Casey, S. Nelson, R. Olariu, J. E. Shellito. 1998. Alveolar macrophage release of tumor necrosis factor-α in chronic alcoholics without liver disease. Alcohol. Clin. Exp. Res. 22: 567-572.
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Brown, L. A., F. L. Harris, D. M. Guidot. 2001. Chronic ethanol ingestion potentiates TNF-α-mediated oxidative stress and apoptosis in rat type II cells. Am. J. Physiol. 281: L377-L386.
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Pan, H. N., R. Sun, B. Jaruga, F. Hong, W. H. Kim, B. Gao. 2006. Chronic ethanol consumption inhibits hepatic natural killer cell activity and accelerates murine cytomegalovirus-induced hepatitis. Alcohol. Clin. Exp. Res. 30: 1615-1623.
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Jerrells, T. R., J. A. Pavlik, J. DeVasure, D. Vidlak, A. Costello, J. M. Strachota, T. A. Wyatt. 2007. Association of chronic alcohol consumption and increased susceptibility to and pathogenic effects of pulmonary infection with respiratory syncytial virus in mice. Alcohol 41: 357-369.
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Crews, F. T., R. Bechara, L. A. Brown, D. M. Guidot, P. Mandrekar, S. Oak, L. Qin, G. Szabo, M. Wheeler, J. Zou. 2006. Cytokines and alcohol. Alcohol. Clin. Exp. Res. 30: 720-730.
