Elsevier

Vaccine

Volume 19, Supplement 1, 8 December 2000, Pages S32-S37
Vaccine

Inflammatory responses in influenza A virus infection

https://doi.org/10.1016/S0264-410X(00)00275-9Get rights and content

Abstract

Influenza A virus causes respiratory tract infections, which are occasionally complicated by secondary bacterial infections. Influenza A virus replicates in epithelial cells and leukocytes resulting in the production of chemokines and cytokines, which favor the extravasation of blood mononuclear cells and the development of antiviral and Th1-type immune response. Influenza A virus-infected respiratory epithelial cells produce limited amounts of chemokines (RANTES, MCP-1, IL-8) and IFN-α/β, whereas monocytes/macrophages readily produce chemokines such as RANTES, MIP-1α, MCP-1, MCP-3, IP-10 and cytokines TNF-α, IL-1β, IL-6, IL-18 and IFN-α/β. The role of influenza A virus-induced inflammatory response in relation to otitis media is being discussed.

Section snippets

Influenza as a disease

Influenza viruses are classified in three types (influenza A, B and C) of which influenza A is clinically the most important one. Influenza A virus is highly contagious and it infects upper respiratory tract of humans in all age groups. It causes infections ranging from sporadic cases to large epidemics or pandemics. The infection is characterized by fever and chills often accompanied by cough, sore throat, headache and myalgia [reviewed in [1]]. The patients may also suffer from general

Influenza A virus and its replication

Influenza viruses are enveloped, negative-stranded RNA viruses, which belong to the family of Orthomyxoviridae. Influenza A virus RNA is composed of eight segmented genes, which encode for ten different proteins; envelope glycoproteins hemagglutinin (HA) and neuraminidase (NA), matrix protein (M1), nucleoprotein (NP), three polymerases (PB1, PB2 and PA), ion channel protein M2, and nonstructural proteins NS1 and NS2 [3]. Influenza A viruses are classified according to their hemagglutinin

Chemokine production

Chemokines are small secretory molecules that are produced by a variety of cells constitutively or in response to microbial infection. Chemokines bind to their specific cell surface receptors in leukocytes, which is followed by a rapid change in cell shape and behavior enabling them to migrate from the blood stream through the vascular endothelium into the site of inflammation [5]. Chemokine receptors are expressed differently on distinct leukocyte subpopulations and chemokines produced vary

Cytokine interplay in innate and adaptive immunity

IFN-α/β functions as a direct antiviral substance. It upregulates the expression of PKR, oligoadenylate synthetases and Mx, which are known to mediate resistance to viral infections [23]. MxA protein has been shown to directly interfere with influenza A virus replication. MxA gene is induced during influenza A virus infection (Fig. 1) [4], [14]. In humans, host's antiviral mechanisms restrict the replication of influenza A virus at early times of infection, which gives the host more time to

Influenza A virus, cytokines and bacterial infections

Influenza A virus infection in the epithelial surfaces is sometimes associated with enhanced bacterial colonization and infection [reviewed in [27], [28]]. Influenza A virus-associated secondary bacterial pneumonia and otitis media [1] are examples of infections, where both viral and bacterial pathogens may be found. The primary target for influenza A virus is the epithelial cell layer of the whole nasopharyngeal area. Virus-infected cells undergo cytolytic or apoptotic death, which impairs

Acknowledgements

We are grateful to Dr Tapani Hovi for critical comments of the manuscript. The expert technical assistance of Valma Mäkinen, Marika Yliselä, and Katja Moilanen is acknowledged. The original work was supported by the Medical Research Council of the Academy of Finland and the Sigrid Juselius Foundation.

References (30)

  • T. Ronni et al.

    Regulation of IFN-alpha/beta, MxA, 2′,5′-oligoadenylate synthetase, and HLA gene expression in influenza A-infected human lung epithelial cells

    J. Immunol.

    (1997)
  • M. Baggiolini

    Chemokines and leukocyte traffic

    Nature

    (1998)
  • M. Adachi et al.

    Expression of cytokines on human bronchial epithelial cells induced by influenza virus A

    Int. Arch. Allergy Immunol.

    (1997)
  • H. Sprenger et al.

    Selective induction of monocyte and not neutrophil-attracting chemokines after influenza A virus infection

    J. Exp. Med.

    (1996)
  • D. Bussfeld et al.

    Differential mononuclear leukocyte attracting chemokine production after stimulation with active and inactivated influenza A virus

    Cell. Immunol.

    (1998)
  • Cited by (228)

    View all citing articles on Scopus
    View full text