Every year some unlucky people get the flu even if they had their chance season. One reason, according to a new study, could be their intestinal bacteria. The researchers showed that, at least in mice, a strong immune response to the vaccine against influenza is partly based on signals from the gut microbes. The findings could help explain variation in response to the vaccine and suggest ways to maximize its effectiveness.
The microbes that inhabit our body-collectively known as the microbiome, can influence everything from obesity risk for food allergies. Recent studies have also shown that the resident microorganisms affect how the immune system reacts to infection. For example, mice with depleted microbiomes appear to be more susceptible to the flu. But it is unclear what role the microbiome in the response to vaccines.
The new evidence emerged from a curious observation that researchers have found in a document of 2011. Bali Pulendran, an immunologist at Emory University in Atlanta, and colleagues were searching for genetic signatures in the blood of those injected with the inactivated influenza vaccine trivalent a mixture of three strains of influenza. They wanted to know if expression of specific genes in the white blood cells of the immune system in correlation with the amount of antibody specific to immunization in the blood, which indicates how well the immune system of a person responds to the shooting, and the degree of protection that person win against future infections. In a long list of genes associated with high immunization response, the researchers found an unexpected one: the gene that codes for a protein called Toll-like receptor 5 (TLR5)
"We thought this should be just one. coincidence, "said Pulendran. TLR5 is a sensor flagellin, a protein that forms the appendages of bacteria. Therefore a receptor that interacts with the bacteria in the gut have nothing to do with the body's response to a virus injected into the muscle? Perhaps, groupthink, B cells white blood cells that produce antibodies, receiving a signal from bacteria that stimulates their activity.
To explore this possibility, the researchers designed a new study using mice. They gave the vaccine against influenza to three different groups of mice genetically engineered to lack the TLR5 gene, the mice without germs, without microorganisms in their bodies, and mice that had spent four weeks water laced with antibiotics to obliterate most of their drinking microbiome.
Seven days after vaccination, all three groups showed significantly reduced levels of vaccine-specific antibodies in their blood to an eightfold reduction compared to control mice vaccinated, the online group reports today ' hui in immunity . The reduction was less marked day 28, antibody levels in the blood appeared to rebound. But when the researchers observed the mice lacking TLR5 the day 85th after vaccination, their antibodies seemed to have plunged again, suggesting that without this bacterial signaling, the effects of the vaccine against the flu over decay quickly.
researchers saw similar results when they gave mice a vaccine against polio, which as the vaccine against influenza, using an inactivated virus and does not contain so-called additives, adjuvants stimulate the body's immune response. Pulendran and his colleagues suggest that these vaccines, the lowest missing adjuvant rely more on bacterial signaling. (They do not see the same results with the live virus in the vaccine against yellow fever, for example.)
No specific types of bacteria seemed more important than another encouraging response to the vaccine. However, other experiments have shown an important role for macrophage-immune cells that exhibit virus pieces to activate B cells and can also recognize flagellin. Preferred explanation of Pulendran that flagellin is unable to pierce the lining of the intestine to circulate throughout the body and activate B cells and macrophages, amplification up to the production of antibodies. But where and how the interaction occurs "is a huge mystery," he said. "We do not have the complete answer."
However, what they do not know presents interesting opportunities for human vaccines. "I think that labor implications are wide enough," said David Artis, an immunologist at Weill Cornell Medical College in New York who was not involved in the study. "It tells us that the microbiome is an additional component [of the vaccine response] that we did not appreciate before. "He notes that people in industrialized countries seem more protection against vaccine against influenza that residents of developing countries, a phenomenon that could be partially explained by variations in their microbiomes, although genetics, diet, and previous infections probably also play a role.
He warned that the group would need to expose mice to flu after vaccination to confirm that the bacterial signals influence the vaccine induces resistance to the virus. But if it does, future vaccines could try to mimic the effect of the bacteria to trigger greater immune response. Several groups have explored as a possible flagellin adjuvant, if Artis suspect this is not the only important microbial protein in the game.
The findings also raise questions about the role of antibiotics in response to the vaccine, said Paul Thomas, an immunologist at St. Jude Children's hospital in Memphis, Tennessee. People taking antibiotics when they could see the vaccinated depressed antibody levels "for a long time after," he said. It suggests a follow-up study to measure the levels of antibodies in people who start antibiotic treatment before getting the vaccine against influenza. Pulendran said his group plans to do this for their next experience.
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