Dual host and pathogen targeting by MEK1/2 inhibitors

Therapeutic strategies that manipulate the host response to infection to reduce inflammation and host driven tissue damage may reduce disease pathogenesis. However, therapeutic approaches that have dual host-modulatory and antimicrobial therapeutic effects remain limited. Mammalian targeting MEK1/2 inhibitor compounds represent one class of small molecules that have now been recognized to have anti-viral effects through disruption of viral replication in epithelial cells and have direct anti-bacterial effects on gram-positive bacteria. MEK1/2 inhibitors elicit anti-inflammatory effects during in vivo infection and injury models that also include models of infection with gram-negative bacteria and parasites. This review aims to summarize progress made in understanding the effects of MEK1/2 inhibitor compounds on host innate immune cells and will highlight experimental models of infection or injury in which MEK1/2 inhibitors have been evaluated. The direct and indirect antimicrobial effects of MEK1/2 inhibitor compounds and the emerging recognition of different roles of MEK1 and MEK2 in programming cellular responses will be identified and discussed.