Nitric oxide contributes to induction of innate immune responses to gram-negative bacteria inDrosophila

Abstract

Studies in mammals uncovered important signaling roles of nitric oxide (NO), and contributions to innate immunity. Suggestions of conservation led us to explore the involvement of NO in Drosophila innate immunity. Inhibition of nitric oxide synthase (NOS) increased larval sensitivity to gram-negative bacterial infection, and abrogated induction of the antimicrobial peptide Diptericin. NOS was up-regulated after infection. Antimicrobial peptide reporters revealed that NO triggered an immune response in uninfected larvae. NO induction of Diptericin reporters in the fat body required immune deficiency (imd) and domino. These findings show that NOS activity is required for a robust innate immune response to gram-negative bacteria, NOS is induced by infection, and NO is sufficient to trigger response in the absence of infection. We propose that NO mediates an early step of the signal transduction pathway, inducing the innate immune response upon natural infection with gram-negative bacteria.

Targeting of TAK1 by the NF-κB protein Relish regulates the JNK-mediated immune response in Drosophila

“…In infected flies, cytokines (Agaisse et al 2003) and other inflammatory mediators (Foley and O'Farrell 2003) mediate secondary responses that have the potential to contribute to JNK activation. Temporal expression patterns and requirements for particular signaling modules could therefore differ from those in S2 cells.…”

Immune Activation of NF-κB and JNK Requires Drosophila TAK1

“…Second, NO has also been implicated in immune signaling in Drosophila. Foley and O'Farrell recently reported that NO is required for transmitting a signal from the site of infection to the fat body, the major organ of immune responsive gene expression (40). Thus, Punch may contribute to the insect immune response in several ways, including protection against stress, melanization of wound sites, and activation of cellular and humoral immunity.…”

Bacterial strategies to overcome insect defences

“…Activation of the Imd pathway induces the expression of different AMPs, such as diptericin, that are active against a range of bacteria and fungi. Moreover, Imd pathway activity in larvae can be modulated by nitric oxide 94 , and this input is mediated by calcineurin, a Ca 2+ -dependent phosphatase 95 .…”