Viral and bacterial infections are a major threat to public health. The emergence and expansion of life-threatening diseases caused by viruses and bacteria (e.g., acquired immune deficiency syndrome, severe acute respiratory syndrome, West Nile and Ebola hemorrhagic fevers, and tuberculosis), together with unmet conventional prevention approaches (e.g., vaccines) highlights the necessity of exploring new strategies that target these deadly pathogens.
Recent studies have revealed that the TAM (Tyro3, Axl and Mer) tyrosine kinase receptors are positioned and function at a critical node of the innate immune response (Rothlin et al., Cell, 2007. 131(6):1124-36; Lemke and Rothlin, Nat. Rev. Immunol., 2008. 8(5):327-36). They are induced in dendritic cells (DCs) and macrophages by Type I interferon (IFN) receptors, which are themselves engaged as a consequence of toll-like receptor (TLR) activation upon encounter with pathogens (e.g., viruses and bacteria). The TAMs then act in concert with type IFN receptors to inactivate both the type I IFN receptors themselves, as well as the TLRs that initially trigger the inflammatory response to pathogens. In this way, the TAMs act as both pleiotropic inhibitors and integrated components of the innate immune response.
The innate immune system fights infection by viruses and bacteria in part through the production of Type I interferons (IFNs), a family of 13 alpha interferons and a single beta interferon (Borden et al., Nat. Rev. Drug Discov., 2007. 6(12):975-90). These agents display broad antiviral and antibacterial activities.
Given the foregoing, it would be desirable to have improved immunoenhancing agents, for instance for use in treating pathogen infections.