Interferon Lambda Inhibits Bacterial Uptake during Influenza Superinfection.
Helen E Rich1,2, Collin C McCourt2, Wen Quan Zheng2
1Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Infection and Immunity
|February 27, 2019
Summary
Interferon lambda (IFN-λ) may worsen bacterial superinfections in influenza patients by reducing neutrophil function, leading to higher bacterial burdens. Caution is advised for IFN-λ as an influenza therapy.
Area of Science:
- Immunology
- Infectious Diseases
- Pulmonology
Background:
- Influenza causes significant mortality and hospitalizations in the US annually.
- Bacterial superinfections, particularly with MRSA and Streptococcus pneumoniae, are common and severe complications of influenza.
- Current treatments for bacterial superinfections are limited by rising antibiotic resistance.
Purpose of the Study:
- To investigate the effect of interferon lambda (IFN-λ) on bacterial clearance during influenza superinfection.
- To evaluate the potential of IFN-λ as a therapeutic agent for influenza in the context of bacterial superinfection.
Main Methods:
- Mice were infected with influenza and subsequently superinfected with MRSA or S. pneumoniae.
- IFN-λ was overexpressed in mice using an adenoviral vector during influenza infection.
- Bacterial burdens, neutrophil function (uptake, motility), and related molecular markers were assessed in lung tissues.
Main Results:
- IFN-λ overexpression during influenza infection led to increased bacterial burdens of MRSA and S. pneumoniae.
- Neutrophil uptake of bacteria was significantly reduced in IFN-λ-treated mice during influenza superinfection.
- IFN-λ treatment did not alter adhesion molecule expression, antimicrobial peptide production, or reactive oxygen species activity.
Conclusions:
- Therapeutic IFN-λ may impair bacterial clearance during influenza superinfection by reducing neutrophil function and motility.
- Caution is warranted regarding the use of IFN-λ as a treatment for influenza due to its potential to exacerbate bacterial superinfections.
Related Concept Videos
00:46Feedback Inhibition
57.1K
Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
57.1K
01:33Bacterial Transformation
59.7K
In 1928, bacteriologist Frederick Griffith worked on a vaccine for pneumonia, which is caused by Streptococcus pneumoniae bacteria. Griffith studied two pneumonia strains in mice: one pathogenic and one non-pathogenic. Only the pathogenic strain killed host mice.
Griffith made an unexpected discovery when he killed the pathogenic strain and mixed its remains with the live, non-pathogenic strain. Not only did the mixture kill host mice, but it also contained living pathogenic bacteria that...
Griffith made an unexpected discovery when he killed the pathogenic strain and mixed its remains with the live, non-pathogenic strain. Not only did the mixture kill host mice, but it also contained living pathogenic bacteria that...
59.7K
01:30Enzyme Inhibition
92.1K
Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
92.1K
02:34Inhibition of Cdk Activity
6.0K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.0K
01:30Bacterial Signaling
40.6K
Bacterial signaling can occur within bacteria (intracellular) or between bacteria (intercellular). At times, a group of bacteria behaves like a community. To achieve this, they engage in quorum sensing, the perception of higher cell density that causes changes in gene expression. Quorum sensing involves both extracellular and intracellular signaling. The signaling cascade starts with a molecule called an autoinducer (AI). Individual bacteria produce AIs that move out of the bacterial cell...
40.6K
01:21Drugs Affecting Neurotransmitter Release or Uptake
1.6K
Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
1.6K