AUTHOR=Huang Chuqin , Xu Rui , Liégeois Samuel , Chen Di , Li Zi , Ferrandon Dominique 

TITLE=Differential Requirements for Mediator Complex Subunits in Drosophila melanogaster Host Defense Against Fungal and Bacterial Pathogens

JOURNAL=Frontiers in Immunology

VOLUME=Volume 11 - 2020

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.478958

DOI=10.3389/fimmu.2020.478958

ISSN=1664-3224

ABSTRACT=The humoral immune response to bacterial or fungal infections in Drosophila relies largely on a transcriptional response mediated by the NF-B pathways Toll and Immune deficiency. Antimicrobial peptides are potent effectors of these pathways and allow the organism to attack invading pathogens. Dorsal-related Immune Factor (Dif), a transcription factor regulated by the Toll pathway, is required in the host defense against fungal and some Gram-positive bacterial infections. The Mediator complex is involved in the initiation of transcription of most RNA polymerase II (PolII)-dependent genes by forming a bridge between transcription factors bound to enhancer regions and the gene promoter region and then recruiting the PolII pre-initiation complex. Mediator is formed by several modules that each comprises several subunits. The Med17 subunit of the head module of Mediator has been shown to be required for the expression of Drosomycin, which encodes a potent antifungal peptide, by binding to Dif. Thus, Mediator is expected to mediate the host defense against pathogens controlled by the Toll pathway-dependent innate immune response. Here, we first focus on the Med31 subunit of the middle module of Mediator and find that it is required in host defense against Aspergillus fumigatus, Enterococcus faecalis, and injected but not topically-applied Metarhizium anisopliae. Indeed, the induction of some Toll-pathway-dependent genes is decreased after a challenge of Med31 RNAi-silenced flies with either A. fumigatus or E. faecalis, while these flies exhibit normal phagocytosis and melanization. However, it is puzzling that host defense against M. anisopliae requires Dif but not Med31 in two distinct infection models. We have further tested all available RNAi lines targeting the expression of other Mediatior subunits by monitoring their survival after challenges to A. fumigatus, E. faecalis, Candida glabrata, or topically-applied M. anisopliae. We report that that the host defense against each of these pathogens involves a distinct set of Mediator subunits with only one subunit for C. glabrata or M. anisopliae or a somewhat extended repertoire for A. fumigatus (7 subunits) and E. faecalis (4 subunits), with limited overlap, mostly Med30 and Med31. Thus, the involvement of Mediator in Drosophila innate immunity is more complex than expected.