The inflammatory response, or inflammation, is our first line of defense against invading microbes and allows the body to heal itself after an injury. “When a wound swells up, turns red and hurts, it may be a sign of inflammation. Inflammation is—very generally speaking—the body’s immune system’s response to stimulus. This can be bacteria colonizing a wound or a splinter piercing your finger, for example. Inflammation happens when the immune system fights against something that may turn out to be harmful.” This type of inflammation, or acute inflammation, is usually beneficial, involves a variety of cells and messenger molecules, requires their cooperation, and is based on the precise coordination of events in which these cells and messenger molecules participate.
In a few instances, however, the inflammatory response can work against the body and facilitate the spread of infection. Here is a case in point, clearly demonstrated by a study recently published in the journal Immunity (Host inflammatory response to mosquito bites enhances severity of arbovirus infection). According to the study, the itchy, red welts that appear after being bitten by a mosquito may help viruses carried by the mosquito itself to spread easily within the bitten organism including, most likely, humans. In other words, “Mosquito bites are not just annoying—they are key for how these viruses spread around your body and cause disease.”
For the study, researchers used mouse models subjected to bites by the Aedes aegypti mosquito, the species that spreads infections such as Zika, dengue and Chikungunya. When a mosquito bites, it injects saliva into the skin. The saliva triggers an inflammatory response in which white blood cells called neutrophils and myeloid cells rush to the site to help clear the damage caused by the bite and prevent the spread of microbes carried by the mosquito.
The researchers injected either Semliki Forest virus (a mosquito-borne virus that is a close relative of Chikungunya virus) or Bunyamwera virus (a genetically unrelated virus that is also transmitted by Aedes mosquitoes) into the skin of mice with or without the presence of a mosquito bite at the injection site, and then compared the reaction. They found that, In the absence of mosquito bites and their accompanying inflammation, the viruses failed to replicate well, whereas the presence of a bite resulted in a high virus level in the skin. Thus, the researchers found that instead of helping, the inflammatory response facilitated virus replication. How? Swelling caused by mosquito bites retains the virus at the inoculation site and causes neutrophils to quickly migrate to the bite site. In turn, neutrophils coordinate a localized innate immune program that encourages the entry of myeloid cells. These myeloid cells are then infected by the viruses injected through the mosquito bite, and allow them to replicate. Thus, neutrophils inadvertently facilitate virus infection.
Clive McKimmie, senior author of the study, said in a press release: “This was a big surprise we didn’t expect. These viruses are not known for infecting immune cells. And sure enough, when we stopped these immune cells coming in, the bite did not enhance the infection anymore.” He also said: “We now want to look at whether medications such as anti-inflammatory creams can stop the virus establishing an infection if used quickly enough after the bite inflammation appears.”
He added that if it is proven to be effective, this approach could work against a multitude of other viruses. “Nobody expected Zika, and before that nobody expected Chikungunya,” he said. “There are estimated to be hundreds of other mosquito-borne viruses out there and it’s hard to predict what’s going to start the next outbreak.”