More than 200 viruses can infect and cause disease in humans, and most individuals will be infected by several viruses over their lifetime. Scientists from the Laboratory of Virology and Infectious Disease at Rockefeller University and the Laboratory of Epigenetics and Immunity at Weill Cornell Medicine collaborated on a study published in Immunity to investigate the impact of previous virus encounters on the immune system’s response to other viruses. The study involved analyzing mice that were first infected with SARS-CoV-2 and then with influenza A virus. Surprisingly, the researchers found that recovery from COVID provided protective effects against the flu due to memory responses developing in innate immune cells called macrophages.
This study revealed that epigenetic changes in macrophages allowed them to remember past infections, leading to a more effective defense against unrelated viruses. While immunological memory has traditionally been associated with adaptive immune cells, the researchers discovered that macrophages were also capable of developing memory responses. What was unique about this memory was that it was not specific to any particular virus. By understanding these mechanisms of innate immune memory, researchers hope to develop therapies that confer broad protection against multiple viruses and enhance our ability to fight off recurring diseases from various pathogens.
The research team found that when a virus enters the body, innate immune cells like macrophages are initially instructed by cytokines to eliminate threats indiscriminately. This general response is followed by a targeted attack from adaptive immune cells like T cells, which specifically recognize and remember the virus for future encounters. However, studies over the past two decades have shown that innate immune responses can also lead to cellular memory and provide protection against unrelated infections. By focusing on widely circulating viruses like SARS-CoV-2 and influenza A virus, the researchers aimed to investigate the long-term consequences of past infections on the immune system.
The study revealed that macrophages in the lungs of COVID-recovered mice underwent epigenetic changes that made antiviral genes more accessible, enhancing their ability to respond to new viral threats. These changes were also observed in samples from humans who had recovered from mild COVID, suggesting a similar mechanism in human immune responses. The memory of previous infections encoded in the epigenetic changes allowed for an altered immune response to future viruses, resulting in reduced disease symptoms and mortality rates when exposed to an unrelated virus like influenza A.
The researchers confirmed their findings by exposing mice to a synthetic mimic of an RNA virus, which triggered similar memory responses in macrophages as seen in COVID-recovered mice. Interestingly, memory-attuned macrophages outperformed adaptive T cells in combating the secondary flu infection, highlighting the significant role of macrophages in driving the immune response. By transferring recovered macrophages into naive mice and infecting them with influenza A virus, the researchers demonstrated the potency of the macrophages’ memory in protecting against severe disease, offering new insights into leveraging innate immune memory in developing antiviral therapies.
Looking ahead, the researchers aim to identify critical factors involved in establishing innate immune memory to develop therapies that offer broad protection against various viruses. This approach could be particularly valuable in preparing for potential pandemics by boosting general antiviral immunity following exposure to new emerging pathogens. While more research is needed, the prospect of developing therapies that enhance our ability to combat a range of respiratory viruses holds promise for improving our pandemic preparedness and managing infectious diseases more effectively in the future.
