Participation of the p38 pathway in Drosophila host defense against pathogenic bacteria and fungi

Abstract

The signaling network of innate immunity in Drosophila is constructed by multiple evolutionarily conserved pathways, including the Toll-or Imd-regulated NF-κB and JNK pathways. The p38 MAPK pathway is evolutionarily conserved in stress responses, but its role in Drosophila host defense is not fully understood. Here we show that the p38 pathway also participates in Drosophila host defense. In comparison with wild-type flies, the sensitivity to microbial infection was slightly higher in the p38a mutant, significantly higher in the p38b mutant, but unchanged in the p38c mutant. The p38b; p38a double-mutant flies were hypersensitive to septic injury. The immunodeficiency of p38b;p38a mutant flies was also demonstrated by hindgut melanization and larvae stage lethality that were induced by microbes naturally presented in fly food. A canonical MAP3K-MKK cascade was found to mediate p38 activation in response to infection in flies. However, neither Toll nor Imd was required for microbe-induced p38 activation. We found that p38-activated heat-shock factor and suppressed JNK collectively contributed to host defense against infection. Together, our data demonstrate that the p38 pathway-mediated stress response contribute to Drosophila host defense against microbial infection.

Hindgut Innate Immunity and Regulation of Fecal Microbiota through Melanization in Insects

“…mutants with developmental defects, some cells were found to be melanized upon infection or stress (30,33), which also provides some support to the existence of PPO in Drosophila hindgut.…”

ERK signaling couples nutrient status to antiviral defense in the insect gut

“…have clear positive roles in immunity spanning flies to humans (JNK and p38) (19)(20)(21)(22). Because genome-wide RNAi screens against viruses in Drosophila have not been optimized to identify antiviral factors but rather required factors (23-25), we performed a directed RNAi screen of 11 core components of these pathways optimized to determine their cell-intrinsic activity against vesicular stomatitis virus (VSV), Sindbis virus (SINV), and Drosophila C virus (DCV) (SI Appendix, Fig.…”

The Digestive Tract of Drosophila melanogaster

“…Gut infection can lead to intestinal damage, which can be caused by bacterial toxins or by an overaggressive, and thus deleterious, immune response. Stress response programs and increased epithelial renewal can then be deployed to repair the intestinal epithelium and maintain the integrity of the gut barrier (21,32,33,90).…”