Local Necrotic Cells Trigger Systemic Immune Activation via Gut Microbiome Dysbiosis in Drosophila

• Published in: Cell reports (Cambridge) 2020-07, Vol.32 (3), p.107938-107938, Article 107938
• Main Authors: Kosakamoto, Hina, Yamauchi, Toshitaka, Akuzawa-Tokita, Yoriko, Nishimura, Kei, Soga, Tomoyoshi, Murakami, Takumi, Mori, Hiroshi, Yamamoto, Kyosuke, Miyazaki, Ryo, Koto, Akiko, Miura, Masayuki, Obata, Fumiaki
• Format: Article
• Language: English
• Subjects: Animals; apoptosis; Colony Count, Microbial; Drosophila; Drosophila melanogaster - immunology; Drosophila melanogaster - microbiology; Dysbiosis - immunology; Dysbiosis - pathology; Gastrointestinal Microbiome - immunology; gluconobacter; Gluconobacter - growth & development; gut microbiota; Immune response; lifespan; metabolome; Necrosis; Signal Transduction; Wings, Animal - immunology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.107938

Necrotic cells elicit an inflammatory response through their endogenous factors with damage-associated molecular patterns. Blocking apoptosis in Drosophila wings leads to the necrosis-driven systemic immune response by unknown mechanisms. Here, we demonstrate that immune activation in response to necrotic cells is mediated by commensal gut microbiota. Removing the microbiome attenuates hyperactivation of the innate immune signaling IMD pathway in necrosis-induced flies. Necrotic cells in wings trigger Gluconobacter expansion in the gut. An isolated Gluconobacter sp. strain is sufficient for pathological IMD activation in necrosis-induced flies, while it is not inflammatory for control animals. In addition, bacterial colonization shifts the host metabolome and shortens the lifespan of necrosis-induced flies. This study shows that local necrosis triggers a pathological systemic inflammatory response through interaction between the host and the dysbiotic gut microbiome. [Display omitted] •Necrotic cells in wings trigger a systemic immune response and shorten the lifespan•Eliminating microbiota diminishes necrosis-induced IMD activation•Gluconobacter sp. increases in the gut in response to wing necrosis•Gluconobacter sp. exacerbates pathologies in necrosis-induced flies Kosakamoto et al. report that wing necrosis induces dysbiotic expansion of Gluconobacter sp. in the gut, which leads to hyperactivation of innate immunity and mortality in Drosophila. This study highlights an interaction between the host and microbial factors triggering a pathological systemic inflammatory response against local necrosis.