Taking AIM at Influenza: The Role of the AIM2 Inflammasome

Influenza A viruses (IAV) are dynamic and highly mutable respiratory pathogens that present persistent public health challenges. Inflammasomes, as components of the innate immune system, play a crucial role in the early detection and response to infections. They react to viral pathogens by triggering inflammation to promote immune defences and initiate repair mechanisms. While a strong response is necessary for early viral control, overactivation of inflammasomes can precipitate harmful hyperinflammatory responses, a defining characteristic observed during severe influenza infections. The Absent in Melanoma 2 (AIM2) inflammasome, traditionally recognised for its role as a DNA sensor, has recently been implicated in the response to RNA viruses, like IAV. Paradoxically, AIM2 deficiency has been linked to both enhanced and reduced vulnerability to IAV infection. This review synthesises the current understanding of AIM2 inflammasome activation during IAV and explores its clinical implications. Understanding the nuances of AIM2's involvement could unveil novel therapeutic avenues for mitigating severe influenza outcomes.