Early IFN type I response: Learning from microbial evasion strategies

•Type I interferon represents the first line of innate host defense against a number of invading pathogens that also instructs adaptive immunity.•Type I interferon induction downstream germ-line-encoded pattern recognition receptors triggers a signaling pathway that results in the expression of hundreds of IFN-stimulated genes with both direct anti-pathogen as well as immunomodulatory activities.•An inverse interference to escape at every step the IFN system is used by pathogens to eventually promote disease progression or establish a chronic infection.•Learning from bacterial and viral escape mechanisms may help in understanding how to cheat the pathogen and fit out the immune system to shift the balance in favor of the host.

Type I interferon (IFN) comprises a class of cytokines first discovered more than 50 years ago and initially characterized for their ability to interfere with viral replication and restrict locally viral propagation. As such, their induction downstream of germ-line encoded pattern recognition receptors (PRRs) upon recognition of pathogen-associated molecular patterns (PAMPs) is a hallmark of the host antiviral response. The acknowledgment that several PAMPs, not just of viral origin, may induce IFN, pinpoints at these molecules as a first line of host defense against a number of invading pathogens. Acting in both autocrine and paracrine manner, IFN interferes with viral replication by inducing hundreds of different IFN-stimulated genes with both direct anti-pathogenic as well as immunomodulatory activities, therefore functioning as a bridge between innate and adaptive immunity. On the other hand an inverse interference to escape the IFN system is largely exploited by pathogens through a number of tactics and tricks aimed at evading, inhibiting or manipulating the IFN pathway, that result in progression of infection or establishment of chronic disease.In this review we discuss the interplay between the IFN system and some selected clinically important and challenging viruses and bacteria, highlighting the wide array of pathogen-triggered molecular mechanisms involved in evasion strategies.