"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 reducing the scavenger cells' appetite: Whenever the immune system recognizes a virus, it gets other immune cells to produce a signaling substance called IFN gamma. 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", Dr. Sabine Stegemann-Koniszewski explains, 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 potential clinical applications. "Missing TLR7 delays the spread of bacteria via the bloodstream", Bruder explains. "Even if we are only talking about a relatively brief time window, 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."
(© Helmholtz-Zentrum für Infektionsforschung / AcademiaNet)