tetano
Editor, Senior Moderator
Infect Immun. 2019 Feb 25. pii: IAI.00114-19. doi: 10.1128/IAI.00114-19. [Epub ahead of print]
[h=1]Interferon Lambda Inhibits Bacterial Uptake During Influenza Super-Infection.[/h] Rich HE[SUP]1,[/SUP][SUP]2[/SUP], McCourt CC[SUP]2[/SUP], Zheng WQ[SUP]2[/SUP], McHugh KJ[SUP]2[/SUP], Robinson KM[SUP]2[/SUP], Wang J[SUP]2[/SUP], Alcorn JF[SUP]3,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza kills 30-40,000 people each year in the United States, and causes ten times as many hospitalizations. A common complication of influenza is bacterial super-infection, which exacerbates morbidity and mortality from the viral illness. Recently, MRSA has emerged as the dominant pathogen found in bacterial super-infection, with Streptococcus pneumoniae a close second. However, clinicians have few tools to treat bacterial super-infection. Current therapy for influenza/bacterial super-infection consists of treating the underlying influenza infection, adding various antibiotics which are increasingly rendered ineffective by rising bacterial multi-drug resistance. Several groups have recently proposed using the antiviral cytokine interferon lambda (IFN-λ) as a therapeutic for influenza, as administration of pegylated IFN-λ improves lung function and survival during influenza by reducing the overabundance of neutrophils in the lung. However, our data suggest that therapeutic IFN-λ impairs bacterial clearance during influenza super-infection. Specifically, mice treated with an adenoviral vector to overexpress IFN-λ during influenza infection exhibited increased bacterial burden upon super-infection with either MRSA or S. pneumoniae Surprisingly, adhesion molecule expression, antimicrobial peptide production, and reactive oxygen species activity were not altered by IFN-λ treatment. However, neutrophil uptake of MRSA and S. pneumoniae was significantly reduced upon IFN-λ treatment during influenza super-infection in vivo Together, these data support the theory that IFN-λ decreases neutrophil motility and function in the influenza-infected lung, which increases bacterial burden during super-infection. Thus, we believe caution should be exercised in the possible future use of IFN-λ as therapy for influenza.
Copyright ? 2019 American Society for Microbiology.
PMID: 30804099 DOI: 10.1128/IAI.00114-19
[h=1]Interferon Lambda Inhibits Bacterial Uptake During Influenza Super-Infection.[/h] Rich HE[SUP]1,[/SUP][SUP]2[/SUP], McCourt CC[SUP]2[/SUP], Zheng WQ[SUP]2[/SUP], McHugh KJ[SUP]2[/SUP], Robinson KM[SUP]2[/SUP], Wang J[SUP]2[/SUP], Alcorn JF[SUP]3,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza kills 30-40,000 people each year in the United States, and causes ten times as many hospitalizations. A common complication of influenza is bacterial super-infection, which exacerbates morbidity and mortality from the viral illness. Recently, MRSA has emerged as the dominant pathogen found in bacterial super-infection, with Streptococcus pneumoniae a close second. However, clinicians have few tools to treat bacterial super-infection. Current therapy for influenza/bacterial super-infection consists of treating the underlying influenza infection, adding various antibiotics which are increasingly rendered ineffective by rising bacterial multi-drug resistance. Several groups have recently proposed using the antiviral cytokine interferon lambda (IFN-λ) as a therapeutic for influenza, as administration of pegylated IFN-λ improves lung function and survival during influenza by reducing the overabundance of neutrophils in the lung. However, our data suggest that therapeutic IFN-λ impairs bacterial clearance during influenza super-infection. Specifically, mice treated with an adenoviral vector to overexpress IFN-λ during influenza infection exhibited increased bacterial burden upon super-infection with either MRSA or S. pneumoniae Surprisingly, adhesion molecule expression, antimicrobial peptide production, and reactive oxygen species activity were not altered by IFN-λ treatment. However, neutrophil uptake of MRSA and S. pneumoniae was significantly reduced upon IFN-λ treatment during influenza super-infection in vivo Together, these data support the theory that IFN-λ decreases neutrophil motility and function in the influenza-infected lung, which increases bacterial burden during super-infection. Thus, we believe caution should be exercised in the possible future use of IFN-λ as therapy for influenza.
Copyright ? 2019 American Society for Microbiology.
PMID: 30804099 DOI: 10.1128/IAI.00114-19