@article{fdi:010048338,
  title = {{A}nopheles gambiae {PGRPLC}-mediated defense against bacteria modulates infections with malaria parasites},
  author = {{M}eister, {S}. and {A}gianian, {B}. and {T}urlure, {F}. and {R}elogio, {A}. and {M}orlais, {I}sabelle and {K}afatos, {F}. {C}. and {C}hristophides, {G}. {K}.},
  editor = {},
  language = {{ENG}},
  abstract = {{R}ecognition of peptidoglycan ({PGN}) is paramount for insect antibacterial defenses. {I}n the fruit fly {D}rosophila melanogaster, the transmembrane {PGN} {R}ecognition {P}rotein {LC} ({PGRP}-{LC}) is a receptor of the {I}md signaling pathway that is activated after infection with bacteria, mainly {G}ram-negative ({G}ram-). {H}ere we demonstrate that bacterial infections of the malaria mosquito {A}nopheles gambiae are sensed by the orthologous {PGRPLC} protein which then activates a signaling pathway that involves the {R}el/{NF}-kappa {B} transcription factor {REL}2. {PGRPLC} signaling leads to transcriptional induction of antimicrobial peptides at early stages of hemolymph infections with the {G}ram-positive ({G}ram+) bacterium {S}taphylococcus aureus, but a different signaling pathway might be used in infections with the {G}ram2 bacterium {E}scherichia coli. {T}he size of mosquito symbiotic bacteria populations and their dramatic proliferation after a bloodmeal, as well as intestinal bacterial infections, are also controlled by {PGRPLC} signaling. {W}e show that this defense response modulates mosquito infection intensities with malaria parasites, both the rodent model parasite, {P}lasmodium berghei, and field isolates of the human parasite, {P}lasmodium falciparum. {W}e propose that the tripartite interaction between mosquito microbial communities, {PGRPLC}-mediated antibacterial defense and infections with {P}lasmodium can be exploited in future interventions aiming to control malaria transmission. {M}olecular analysis and structural modeling provided mechanistic insights for the function of {PGRPLC}. {A}lternative splicing of {PGRPLC} transcripts produces three main isoforms, of which {PGRPLC}3 appears to have a key role in the resistance to bacteria and modulation of {P}lasmodium infections. {S}tructural modeling indicates that {PGRPLC}3 is capable of binding monomeric {PGN} muropeptides but unable to initiate dimerization with other isoforms. {A} dual role of this isoform is hypothesized: it sequesters monomeric {PGN} dampening weak signals and locks other {PGRPLC} isoforms in binary immunostimulatory complexes further enhancing strong signals.},
  keywords = {},
  booktitle = {},
  journal = {{P}lo{S} {P}athogens},
  volume = {5},
  numero = {8},
  pages = {art. e1000542},
  ISSN = {1553-7366},
  year = {2009},
  DOI = {10.1371/journal.ppat.1000542},
  URL = {https://www.documentation.ird.fr/hor/fdi:010048338},
}