J Clin Invest. Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice.

[Giuseppe]

Abstract. Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice.

Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice

[Full PDF Document: LINK. EDITED.]

Arash Shahangian, 1,2 Edward K. Chow, 3 Xiaoli Tian, 4 Jason R. Kang, 1 Amir Ghaffari, 1,2 Su Y. Liu, 1,2 John A. Belperio, 4 Genhong Cheng, 1,5 and Jane C. Deng 4

1 Department of Microbiology, Immunology and Molecular Genetics, and
2 Medical Scientist Training Program, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
3 G.W. Hooper Foundation, UCSF, San Francisco, California, USA.
4 Division of Pulmonary and Critical Care Medicine and 5Molecular Biology Institute, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.


Abstract.


Influenza-related complications continue to be a major cause of mortality worldwide. Due to unclear mechanisms, a substantial number of influenza-related deaths result from bacterial superinfections, particularly secondary pneumococcal pneumonia. Here, we report what we believe to be a novel mechanism by which influenza-induced type I IFNs sensitize hosts to secondary bacterial infections. Influenza-infected mice deficient for type I IFN-α/β receptor signaling (Ifnar?/? mice) had improved survival and clearance of secondary Streptococcus pneumoniae infection from the lungs and blood, as compared with similarly infected wild-type animals.

The less effective response in wild-type mice seemed to be attributable to impaired production of neutrophil chemoattractants KC (also known as Cxcl1) and Mip2 (also known as Cxcl2) following secondary challenge with S. pneumoniae. This resulted in inadequate neutrophil responses during the early phase of host defense against secondary bacterial infection.

Indeed, influenza-infected wild-type mice cleared secondary pneumococcal pneumonia after pulmonary administration of exogenous KC and Mip2, whereas neutralization of Cxcr2, the common receptor for KC and Mip2, reversed the protective phenotype observed in Ifnar?/? mice.

These data may underscore the importance of the type I IFN inhibitory pathway on CXC chemokine production.

Collectively, these findings highlight what we believe to be a novel mechanism by which the antiviral response to influenza sensitizes hosts to secondary bacterial pneumonia.


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[Giuseppe]

Re: J Clin Invest. Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice.

The immune response to influenza virus isn't 'all good' (EurekAlert, edited)

The immune response to influenza virus isn't 'all good'


Complications following infection with the virus that causes flu (influenza virus) are one of the top ten causes of death in the United States.


Although infection with influenza virus can directly cause death, many deaths following infection with influenza virus occur because the individual develops pneumonia due to secondary infection with bacteria such as Streptococcus pneumoniae.

How influenza makes individuals more sensitive to pneumonia-causing secondary bacterial infections is not well understood.

However, Jane Deng and colleagues, at the University of California, Los Angeles, have now determined, through studies in mice, one mechanism by which influenza might sensitize individuals to secondary bacterial pneumonia.

In the study, it was found that molecules known as type I IFNs, which are key mediators of the antiviral immune response initiated by infection with influenza virus, impaired the ability of mice to mount an adequate immune response to subsequent pneumonia-causing bacterial infection.

In particular, the type I IFNs decreased production of soluble factors that attract neutrophils, immune cells central to the initial antibacterial immune response, to sites of bacterial infection.

The authors therefore suggest that the pathway uncovered in their study might provide a new avenue of research for those developing ways to combat pneumonia following infection with influenza virus.

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TITLE:
Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice

AUTHOR CONTACT:
Jane C. Deng
David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Phone: (310) 983-3446; Fax: (310) 206-8622; E-mail: jdeng@mednet.ucla.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=35412
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<cite cite="http://www.eurekalert.org/pub_releases/2009-06/joci-tir052809.php">The immune response to influenza virus isn't 'all good'</cite>