Role of Macrophage Cytokines in Influenza A Virus lnfections

doi:10.1016/S0171-2985(11)80365-7

Immunobiology

Volume 189, Issues 3–4, November 1993, Pages 340-355

https://doi.org/10.1016/S0171-2985(11)80365-7 Get rights and content

Abstract

Human monocytes and murine macrophages were found to be susceptible to infection by influenza A virus. Although virus replication was low, infection led to cell death which was characterized by an extreme intracellular vacuolization. Most importantly, influenza A virus infection was accompanied by a particular pattern of cytokine release. Whereas IL-1β, IL-6 and TNF-α production was dependent on exposure to infectious virus, IFN-α/β release was also induced by UV-inactivated virus. Although influenza A virus infection alone induced a substantial cytokine mRNA accumulation, translation into bioactive cytokine protein was rather limited. However, addition of low LPS concentrations was capable of strongly potentiating cytokine release from virus-infected cells. Thus, in a first step, an influenza A virus infection primes mononuclear phagocytes by leading to an accumulation of cytokine mRNA which, in a second step, may be readily translated into bioactive cytokines when triggering signals such as LPS are available. These findings suggest that influenza A virus represents an ultimately fatal macrophage activating factor which, when inducing moderate amounts of cytokines, may be beneficial by mounting an immediate antiviral response, but which may cause adverse effects when cytokine release is highly elevated by bacterial products.

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: This work was supported by the Deutsche Forschungsgemeinschaft (Ge354/8-2).

^a: Dr. Diethard Gemsa, Institute of Immunology, Philipps University, Postfach 2360, 35011 Marburg, Germany

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Role of Macrophage Cytokines in Influenza A Virus lnfections

Abstract

Clin. Immunol. Immunopathol.

Immunobiol.

Adv. Virus Res.

Viruses perturb lymphocyte functions: Selected principles characterizing virus-induced immunosuppression

Ann. Rev. Immunol.

Tumor necrosis factor induction by Sendai virus

J. Immunol.

Sendai virus induces high levels of tumor necrosis factor mRNA in human peripheral blood leukocytes

Nucleic Acids Res.

Coordinate viral induction of tumor necrosis factor α and interferon β in human B cells and monocytes

Proc. Natl. Acad. Sci. USA

Cytomegalovirus infection stimulates expression of monocyte-associated mediator genes

J. Immun.

Newcastle disease virus as an antineoplastic agent: induction of tumor necrosis factor-α and augmentation of its cytotoxicity

JNCI

Production of tumor necrosis factor α and interleukin 1β by monocytic cells infected with human immunodeficiency virus

J. Clin. Invest.

Spontaneous cytotoxicity and tumor necrosis production by peripheral blood monocytes from AIDS patients

J. Immunol.

Differential gene expression of IFN-α and tumor necrosis factor-α in peripheral blood mononuclear cells from patients with AIDS related complex and AIDS

J. Immunol.

Tumor necrosis factor-α production of influenza A virus-infected macrophages and potentiating effect of lipopolysaccharides

J. Immunol.

Influenza A virus infection of macrophages

Enhanced tumor necrosis-α (TNF-α) gene expression and lipopolysaccharide-triggered TNF-α release. J. Immunol.

Activation of mononuclear phagocytes by granulocyte-macrophage colony-stimulating factor

Production of interleukin 1 and tumor necrosis factor activities in bronchoalveolar washings following infection of mice by influenza virus

J. Gen. Virol.