A tissue communication network coordinating innate immune response during muscle stress

Abstract

Complex tissue communication networks function throughout an organism's lifespan to maintain tissue homeostasis. Using the genetic model Drosophila melanogaster, we have defined a network of immune responses that are activated following the induction of muscle stresses, including hypercontraction, detachment and oxidative stress. Of these stressors, loss of the genes that cause muscle detachment produced the strongest levels of JAK-STAT activation. In one of these mutants, fondue (fon), we also observe hemocyte recruitment and the accumulation of melanin at muscle attachment sites (MASs), indicating a broad involvement of innate immune responses upon muscle detachment. Loss of fon results in pathogen-independent Toll signaling in the fat body and increased expression of the Toll-dependent antimicrobial peptide Drosomycin. Interestingly, genetic interactions between fon and various Toll pathway components enhance muscle detachment. Finally, we show that JAK-STAT and Toll signaling are capable of reciprocal activation in larval tissues. We propose a model of tissue communication for the integration of immune responses at the local and systemic level in response to altered muscle physiology.

Intramacrophage ROS Primes the Innate Immune System via JAK/STAT and Toll Activation

“…Similar to mammals, our study demonstrates that the Toll pathway can be activated in hemocytes in the absence of any pathogens or microbes. The Toll pathway has been linked to resistance against septic injury and is also activated in the fat body of larvae upon muscle damage (Green et al, 2018). In fly larvae, wasp parasitism increased ROS levels in the lymph gland and Following injury, hemocytes respond to the damage signal H 2 O 2 , which is produced by the NADPH oxidase Duox, through the kinase Src42A and its downstream targets Shark and Draper.…”

Drosophila NUAK functions with Starvin/BAG3 in autophagic protein turnover

“…Wandering L3 larvae were dissected to isolate muscle fillets and fixed in 4% formaldehyde as described [32,34,82]. Tissues were stained with the following primary antibodies: mouse anti-TM (1:50, Babraham Institute, Cambridge, UK), mouse anti-MHC (1:500, Susan Abmayr) [83], rabbit anti-Mlp84B (1:50, Kathleen Clark) [33], rabbit anti-Fil (1:300, Lynn Cooley) [84], rat anti-CryAB (1:400, Teresa Jagla) [39], mouse anti-Ub (1:300, Enzo Life Sciences, Farmingdale, NY), and rabbit anti-ref 2…”

Comparative RNA-Seq analyses of Drosophila plasmatocytes reveal gene specific signatures in response to clean injury and septic injury

“…Furthermore, hemocytes produce enzymes essential to the melanization reaction [9,10]. Recent evidence shows that Drosophila blood cells contribute not only to immunity and wound healing, but are also central to host metabolism [11][12][13][14]. That an excessive number of hemocytes can be detrimental to flies raised on a poor diet shows that hemocyte number must be tightly regulated [15].…”