Infection with influenza A virus (IAV) results in an acute respiratory disease with a highly variable pathogenesis. Viral infection triggers various inflammatory mechanisms that promote viral clearance on the one hand but can have deleterious effects on pulmonary tissue integrity on the other hand. A detailed knowledge of the mechanisms involved in the antiviral immune responses to IAV is key for a better understanding the concept of host susceptibility and eventually for the design of future therapeutic treatment strategies. In their latest publication in Mucosal Immunology, Yang et al. highlight a pivotal role of the transcription factor nuclear matrix protein 4 (NMP4) in driving inflammatory recruitment of monocytes and neutrophils and increasing disease severity during IAV infection. 1

The pathogenesis of IAV is dependent on both the viral strain 2 and host-intrinsic factors (eg, genetic variants, 3 immune and/or nutritional status 4). During IAV infection, the immune system is acutely challenged with balancing the tasks “limiting pathogen spread” vs.“limiting tissue damage”, and severe courses of disease