Researchers have identified a molecular switch that impacts immune responses to viral infections, and whether or not protective antibodies are produced.
The team also made the surprising discovery that the immune system protects against different viruses via distinct pathways. Their findings could lead to better strategies to develop vaccines for previously hard-to-prevent viruses. The research was published in the journal Cell Reports.
The team discovered that T-bet was an essential switch that enabled T cells to stimulate antibody production in response to viral infections. "The level of T-bet in T cells is influenced by factors such as how a virus enters the body, and how much inflammation it triggers in its early stages. This in turn influences the immune response to the virus," the author said.
These findings reconcile a controversy in the field about how the immune system can distinguish between different viral infections, and respond in distinct ways. "We compared the role of the T-bet switch in immune responses to two viruses, influenza and LCMV, a virus that can cause meningitis," another author said.
"These viruses are thought to activate similar immune cells, yet we demonstrated specific changes between the responses could lead to very different amounts of protective antibodies. We showed that T-bet was critical for scaling how much antibody production occurred in response to a viral infection."
The authors demonstrate that T-bet expression by either TFH or GC B cells independently drives antibody isotype class switching. Specifically, T cell-specific loss of T-bet promotes IgG1, whereas B cell-specific loss of T-bet inhibits IgG2a/c switching. Combined, this work highlights that the context-dependent induction of T-bet instructs the development of protective, neutralizing antibodies following viral infection or vaccination.
The findings could underpin the development of more effective vaccines against viruses. "Most current vaccines to infectious diseases rely on robust and long-lived antibody production. If we can understand the precise triggers controlling how much antibody is produced in response to an infection, we should be able to develop vaccines that act similarly to stimulate protective antibody production," the author said.
How body responds to different viral infections
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