Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites.

Recognition of peptidoglycan (PGN) is paramount for insect antibacterial defenses. In the fruit fly Drosophila melanogaster, the transmembrane PGN Recognition Protein LC (PGRP-LC) is a receptor of the Imd signaling pathway that is activated after infection with bacteria, mainly Gram-negative (Gram-)...

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Autores principales:	Stephan Meister, Bogos Agianian, Fanny Turlure, Angela Relógio, Isabelle Morlais, Fotis C Kafatos, George K Christophides
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/56e61d6507ca4260b7cd69b220a8f9af
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spelling	oai:doaj.org-article:56e61d6507ca4260b7cd69b220a8f9af2021-12-02T19:59:46ZAnopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites.1553-73661553-737410.1371/journal.ppat.1000542https://doaj.org/article/56e61d6507ca4260b7cd69b220a8f9af2009-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19662170/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Recognition of peptidoglycan (PGN) is paramount for insect antibacterial defenses. In the fruit fly Drosophila melanogaster, the transmembrane PGN Recognition Protein LC (PGRP-LC) is a receptor of the Imd signaling pathway that is activated after infection with bacteria, mainly Gram-negative (Gram-). Here we demonstrate that bacterial infections of the malaria mosquito Anopheles gambiae are sensed by the orthologous PGRPLC protein which then activates a signaling pathway that involves the Rel/NF-kappaB transcription factor REL2. PGRPLC signaling leads to transcriptional induction of antimicrobial peptides at early stages of hemolymph infections with the Gram-positive (Gram+) bacterium Staphylococcus aureus, but a different signaling pathway might be used in infections with the Gram- bacterium Escherichia coli. The 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. We show that this defense response modulates mosquito infection intensities with malaria parasites, both the rodent model parasite, Plasmodium berghei, and field isolates of the human parasite, Plasmodium falciparum. We propose that the tripartite interaction between mosquito microbial communities, PGRPLC-mediated antibacterial defense and infections with Plasmodium can be exploited in future interventions aiming to control malaria transmission. Molecular analysis and structural modeling provided mechanistic insights for the function of PGRPLC. Alternative splicing of PGRPLC transcripts produces three main isoforms, of which PGRPLC3 appears to have a key role in the resistance to bacteria and modulation of Plasmodium infections. Structural modeling indicates that PGRPLC3 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.Stephan MeisterBogos AgianianFanny TurlureAngela RelógioIsabelle MorlaisFotis C KafatosGeorge K ChristophidesPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 8, p e1000542 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Stephan Meister Bogos Agianian Fanny Turlure Angela Relógio Isabelle Morlais Fotis C Kafatos George K Christophides Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites.
description	Recognition of peptidoglycan (PGN) is paramount for insect antibacterial defenses. In the fruit fly Drosophila melanogaster, the transmembrane PGN Recognition Protein LC (PGRP-LC) is a receptor of the Imd signaling pathway that is activated after infection with bacteria, mainly Gram-negative (Gram-). Here we demonstrate that bacterial infections of the malaria mosquito Anopheles gambiae are sensed by the orthologous PGRPLC protein which then activates a signaling pathway that involves the Rel/NF-kappaB transcription factor REL2. PGRPLC signaling leads to transcriptional induction of antimicrobial peptides at early stages of hemolymph infections with the Gram-positive (Gram+) bacterium Staphylococcus aureus, but a different signaling pathway might be used in infections with the Gram- bacterium Escherichia coli. The 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. We show that this defense response modulates mosquito infection intensities with malaria parasites, both the rodent model parasite, Plasmodium berghei, and field isolates of the human parasite, Plasmodium falciparum. We propose that the tripartite interaction between mosquito microbial communities, PGRPLC-mediated antibacterial defense and infections with Plasmodium can be exploited in future interventions aiming to control malaria transmission. Molecular analysis and structural modeling provided mechanistic insights for the function of PGRPLC. Alternative splicing of PGRPLC transcripts produces three main isoforms, of which PGRPLC3 appears to have a key role in the resistance to bacteria and modulation of Plasmodium infections. Structural modeling indicates that PGRPLC3 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.
format	article
author	Stephan Meister Bogos Agianian Fanny Turlure Angela Relógio Isabelle Morlais Fotis C Kafatos George K Christophides
author_facet	Stephan Meister Bogos Agianian Fanny Turlure Angela Relógio Isabelle Morlais Fotis C Kafatos George K Christophides
author_sort	Stephan Meister
title	Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites.
title_short	Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites.
title_full	Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites.
title_fullStr	Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites.
title_full_unstemmed	Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites.
title_sort	anopheles gambiae pgrplc-mediated defense against bacteria modulates infections with malaria parasites.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/56e61d6507ca4260b7cd69b220a8f9af
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Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites.

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