Appetite suppressant for scavenger cells: Influenza curbs part of the immune system and abets bacterial infections
A scavenger cell of the immune system ingests bacteria (shown in green). During an influenza infection, the macrophages appetite is curbed. Credit: Manfred Rohde/HZI
When infected with influenza, the body becomes an easy target for bacteria. The flu virus alters the host's immune system and compromises its capacity to effectively fight off bacterial infections. Now, a team of immunologists at the Helmholtz Centre for Infection Research (HZI) and cooperation partners has discovered that an immune system molecule called TLR7 is partly to blame. The molecule recognizes the viral genome – and then signals scavenger cells of the immune system to ingest fewer bacteria. The researchers published their findings in the Journal of Innate Immunity.
The flu is not just a seasonal illness during the winter months. In the past, there have been several flu pandemics that have claimed the lives of millions. By now, we know that during the course of the disease, many people not only get sick from the flu itself but also from bacterial pathogens like the much-feared pneumococci, the bacteria causing pneumonia. In many cases, such "superinfections" can cause the disease to take a turn for the worse. In fact, during the Spanish Flu of 1918 to 1920, they were responsible for the majority of deaths. Why an infection with the flu virus increases the risk for superinfections is still poorly understood. Now, a group of scientists from HZI, the University Hospital of the Otto von Guericke University Magdeburg, the Essen University Hospital, the Karolinska Institute in Stockholm, Sweden, as well as further research institutions have discovered one more detail on how the virus manipulates the immune system.
They focused on TLR7, a molecule that is found in different cells of the body. TLR7 is capable of recognizing viral genetic material. As it turns out, TLR7 has an unwanted side effect, too: During a flu infection, it appears to undermine the body's innate ability to fight off bacteria, thereby increasing the chance of a superinfection. The researchers made their discovery when they examined how superinfected mice were dealing with the bacterium Streptococcus pneumoniae, the pneumonia pathogen. The scientists colored the bacteria and measured how many of them were taken up by scavenger cells of the immune system called macrophages. The macrophages of TLR7-deficient mice had a bigger appetite and eliminated larger numbers of bacteria when infected with the flu than those of mice with the intact viral sensor. "Without TLR7, it takes longer before influenza-infected mice reach the critical point where they are no longer able to cope with the bacterial infection," explains Prof. Dunja Bruder, head of HZI's "Immune Regulation Group" and professor of infection immunology at the University Hospital Magdeburg.
The scientists also have an idea about how TLR7 may be curtailing the scavenger cells' appetite: Whenever the immune system recognizes a virus, it gets other immune cells to produce a signaling substance called IFN gamma. It is already known that this substance inhibits macrophages in the lungs, causing them to eliminate fewer bacteria. As part of their study, the researchers discovered another indication of this special relationship: In TLR7-deficient animals they found smaller quantities of the IFN gamma messenger substance. The consequence might be that macrophages have a bigger appetite and that therefore bacterial entry into the bloodstream is delayed.
"Our results confirm that in the long run the flu virus suppresses the body's ability to defend itself against bacteria. Presumably, this is an unwanted side effect of the viral infection," speculates Dr. Stegemann-Koniszewski, the study's first author.
"Unfortunately, it is rather difficult to intervene therapeutically. At first glance, it seems obvious to inhibit TLR7 during influenza so that the macrophages are actually able to get rid of the bacteria. However, this could have unforeseen repercussions as TLR7 and IFN gamma are both part of a tightly regulated immunological network," explains Prof. Matthias Gunzer, former research group leader at the HZI and currently a professor at Essen University Hospital.
Even if a lack of TLR7 cannot by itself ward off a bacterial superinfection, the researchers' findings could still lead to highly promising potential clinical applications. "Missing TLR7 delays the spread of bacteria via the bloodstream," says Bruder. "Even if we are only talking about a relatively brief window of time, this might be our critical opportunity for keeping a seriously ill patient alive. The more time doctors have to choose the right antibiotic for their patient, the better the chances of a successful treatment."
More information: Sabine Stegemann-Koniszewski, Marcus Gereke, Sofia Orrskog, Stefan Lienenklaus, Bastian Pasche, Sophie R. Bader, Achim D. Gruber, Shizuo Akira, Siegfried Weiss, Birgitta Henriques-Normark, Dunja Bruder, Matthias Gunzer, TLR7 contributes to the rapid progression but not to the overall fatal outcome of secondary pneumococcal disease following influenza A virus infection, Journal of Innate Immunity, 2012. DOI: 10.1159/000345112
Provided by Helmholtz Association of German Research Centres
- Brothers in arms Mar 17, 2009 | not rated yet | 0
- Molecules help the immune system to detect cells infected with West Nile virus Feb 05, 2009 | not rated yet | 0
- Scientists show lack of single protein results in persistent viral infection Jun 13, 2012 | not rated yet | 0
- Flu helps spread pneumonia Apr 11, 2011 | not rated yet | 0
- Resistant mice provide clues about successful immune response to retroviruses Jun 30, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Change in momentum when a body is thrown up and falls back down.
3 hours ago Say, a body of mass 'm' is thrown at a certain angle with the vertical with certain initial velocity 'u'. The initial momentum of this object is mu....
change in speed and wavelength of light while travelling from one med
3 hours ago what is the mechanism by which light changes its speed and wavelength while travelling from one medium to other. I know it is c/n or lamda/n and know...
Calculus of Variation - Classical Mechanics
6 hours ago I'm reading Classical Mechanics (Taylor), and the 6th chapter is a basic introduction to calculus of variations. I'm super confused :confused: ...
Frictional Force Equation Doesn't Make Sense
6 hours ago Frictional Force is mathematically defined as: Ff = μ*m*g*cos(θ) , where μ is the coefficient of friction, m is the mass of the object, g is...
Calculating Steam Pressure in Closed Container
11 hours ago I am trying to calculate the volume of liquid water i need to place in a sealed container in order to obtain 10 psi of steam pressure in that closed...
Learning curve of Electromagnetism?
16 hours ago I'm taking a first year physics course and have been having a little trouble with the basics of newtons laws and forces and whatnot, though nothing...
- More from Physics Forums - Classical Physics
More news stories
Raising hopes for cell-based therapies, UC San Francisco researchers have created the first functioning human thymus tissue from embryonic stem cells in the laboratory. The researchers showed that, in mice, ...
Immunology May 16, 2013 | 4.8 / 5 (5) | 0 |
Researchers from CNRS, Université Toulouse III - Paul Sabatier and IRD have elucidated new molecular mechanisms involved in resistance to visceral leishmaniasis, a serious parasitic infection. They have shown that dectin-1 ...
Immunology May 16, 2013 | not rated yet | 0
Women's immune systems age more slowly than men's, suggests research in BioMed Central's open access journal Immunity & Ageing. The slower decline in a woman's immune system may contribute to women living longer than men. ...
Immunology May 14, 2013 | not rated yet | 0
Newly described type of immune cell and T cells share similar path to maturity, according to new study
(Medical Xpress)—Labs around the world, and a core group at Penn, have been studying recently described populations of immune cells called innate lymphoid cells (ILCs). Some researchers liken them to foot soldiers that ...
Immunology May 14, 2013 | 5 / 5 (3) | 0 |
(Medical Xpress)—Cytokines are molecules produced by immune cells that induce the migration of other cells to sites of infection or injury, promote the production of anti-microbial agents, and signal the production of inflammatory ...
Immunology May 13, 2013 | 5 / 5 (1) | 0 |
Regular consumption of coffee is associated with a reduced risk of primary sclerosing cholangitis (PSC), an autoimmune liver disease, Mayo Clinic research shows. The findings were being presented at the Digestive Disease ...
5 hours ago | not rated yet | 0 |
Patients with treatment-resistant major depression saw dramatic improvement in their illness after treatment with ketamine, an anesthetic, according to the largest ketamine clinical trial to-date led by researchers from the ...
5 hours ago | 4.5 / 5 (2) | 0 |
Research presented at Digestive Disease Week (DDW) explores new methods for managing digestive health through diet and lifestyle.
5 hours ago | not rated yet | 0
The use of a smartphone application significantly improves patients' preparation for a colonoscopy, according to new research presented today at Digestive Disease Week (DDW). The preparation process, which begins days in ...
5 hours ago | not rated yet | 0
There are significant cost and risk factors associated with two procedures commonly used to diagnose or treat gastrointestinal problems, according to research presented at Digestive Disease Week (DDW).
5 hours ago | not rated yet | 0
An increasing number of U.S. children are experiencing gastrointestinal issues that require interventions to resolve, according to research presented at Digestive Disease Week (DDW).
20 hours ago | not rated yet | 0 |