From gatekeeper to target: MAPK cascades as control circuits at the insect-microbe interface.

Mitogen-activated protein kinase (MAPK) signaling cascades are conserved modules that orchestrate multiple processes, including immunity, stress adaptation, and tissue homeostasis. In insects, MAPK pathways function as central regulatory circuits, coordinating defense responses and resistance mechanisms against diverse pathogens. MAPK cascades couple damage sensing in the gut epithelium to intestinal regeneration, pathogen/microbiota stability, cellular and humoral immune responses, and immune homeostasis. Consequently, a wide range of pathogens (parasites, viruses, and bacteria) target, suppress, or hijack key regulatory bottlenecks in MAPK networks to promote pathogen invasion, replication, or transmission. Understanding this molecular arms race provides insight into fundamental principles governing insect-microbe coevolution and reveals critical regulatory nodes that could be exploited to develop innovative strategies for controlling insect pests and vector-borne diseases.