biostudies-literatureUnknown21(9)Audi AIn the Afrotropical malaria vector Anopheles gambiae s.l., the Imd pathway plays pleiotropic roles in immunity, including resistance to malaria parasites, that are mediated by its NF-κB transcription factor Rel2. Rel2 exists as a full-length form (Rel2-F) containing the Rel-homology domain (RHD) and the C-terminal inhibitory ankyrin (Ank) and death domains (DD), and a shorter alternatively spliced form (Rel2-S) proposed to encode a constitutively active protein containing only the RHD. Despite its important roles in immunity, there are still multiple uncertainties concerning the identity and function of key components of the pathway as well as its overall contribution to mosquito resistance to systemic bacterial infections. Here, we show that Rel2 is critical for limiting the burden of GraPLoS pathogense1013527https://www.ebi.ac.uk/biostudies/studies/S-EPMC12459809biostudies-literatureA PGRPLC1/Rel2-F axis controls Anopheles gambiae resistance to systemic infections with Gram-positive bacteria containing Lys-type peptidoglycan.PMC12459809Audi AZeineddine SOsta MAJaber SfalseA PGRPLC1/Rel2-F axis controls Anopheles gambiae resistance to systemic infections with Gram-positive bacteria containing Lys-type peptidoglycan.In the Afrotropical malaria vector Anopheles gambiae s.l., the Imd pathway plays pleiotropic roles in immunity, including resistance to malaria parasites, that are mediated by its NF-κB transcription factor Rel2. Rel2 exists as a full-length form (Rel2-F) containing the Rel-homology domain (RHD) and the C-terminal inhibitory ankyrin (Ank) and death domains (DD), and a shorter alternatively spliced form (Rel2-S) proposed to encode a constitutively active protein containing only the RHD. Despite its important roles in immunity, there are still multiple uncertainties concerning the identity and function of key components of the pathway as well as its overall contribution to mosquito resistance to systemic bacterial infections. Here, we show that Rel2 is critical for limiting the burden of Gra2025-01-01T00:00:00Z2025 Sep2026-06-03T19:50:07.295Z2026-05-01T03:10:46.505ZS-EPMC124598094097195710.1371/journal.ppat.1013527