A Tissue Communication Network Coordinating Innate Immune Response During Muscle Stress
Tissue communication is required for maintaining organismal homeostasis during development. The coordination of metabolism, immune activation, and circadian rhythms typify the complex tissue networks necessary for organismal health. Our lab is using the Drosophila muscle attachment site (MAS) as a model to understand the connection between innate immune activation and muscle maintenance. A pupal lethal screen for abnormal pupal morphology revealed a previously unknown role for the extracellular matrix (ECM) protein Fondue (Fon), in muscle development. Previously characterized for its role in clot integrity, loss of fon caused a reduction in larval locomotion due to the detachment of body wall muscles. More interestingly, a sensitized background screen revealed a subset of coagulation proteins, Fon, Tiggrin (Tig), and Larval Serum Protein 1 γ (Lsp1γ), that are secreted from the fat body and incorporated into MASs for stabilization. In fon mutants with muscle detachment, we also observed abnormal melanin accumulation along the MAS, pathogen-independent translocation of Dorsal (Dl) in the fat body, constituitive expression of the antimicrobial peptide (AMP) drosomycin, and recruitment of hemocytes to damaged muscle. In a fon-sensitized background assay, we identified genetic interactions between fon and Toll pathway genes, including loss of the NFκB inhibitor/IκB, cactus, and overactivation of SPE which enhance muscle detachment. We also analyzed Toll activation in the absence of hemocytes, and our data suggests that hemocytes are not necessary for Toll activation upon muscle detachment. Understanding the mechanisms by which muscle detachment or stress activate the innate immune system will advance our knowledge of how tissue stresses can be sensed and the molecular mechanisms eliciting multi-tissue responses.