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

Stephan Meister, Bogos Agianian, Fanny Turlure, Angela Relógio, Isabelle Morlais, Fotis C. Kafatos, George K. Christophides

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

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-kB 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.

Original languageEnglish (US)
Article numbere1000542
JournalPLoS Pathogens
Volume5
Issue number8
DOIs
StatePublished - Aug 2009
Externally publishedYes

Fingerprint

Anopheles gambiae
Malaria
Parasites
Culicidae
Peptidoglycan
Bacteria
Protein Isoforms
Infection
Bacterial Infections
Plasmodium berghei
Hemolymph
NF-kappa B
Alternative Splicing
Dimerization
Gram-Positive Bacteria
Plasmodium falciparum
Drosophila melanogaster
Gram-Negative Bacteria
Diptera
Insects

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Immunology
  • Microbiology
  • Parasitology
  • Virology

Cite this

Meister, S., Agianian, B., Turlure, F., Relógio, A., Morlais, I., Kafatos, F. C., & Christophides, G. K. (2009). Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites. PLoS Pathogens, 5(8), [e1000542]. https://doi.org/10.1371/journal.ppat.1000542

Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites. / Meister, Stephan; Agianian, Bogos; Turlure, Fanny; Relógio, Angela; Morlais, Isabelle; Kafatos, Fotis C.; Christophides, George K.

In: PLoS Pathogens, Vol. 5, No. 8, e1000542, 08.2009.

Research output: Contribution to journalArticle

Meister, S, Agianian, B, Turlure, F, Relógio, A, Morlais, I, Kafatos, FC & Christophides, GK 2009, 'Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites', PLoS Pathogens, vol. 5, no. 8, e1000542. https://doi.org/10.1371/journal.ppat.1000542
Meister, Stephan ; Agianian, Bogos ; Turlure, Fanny ; Relógio, Angela ; Morlais, Isabelle ; Kafatos, Fotis C. ; Christophides, George K. / Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites. In: PLoS Pathogens. 2009 ; Vol. 5, No. 8.
@article{ff68d5a609084ccbbc2bc550b4bf7456,
title = "Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites",
abstract = "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-kB 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.",
author = "Stephan Meister and Bogos Agianian and Fanny Turlure and Angela Rel{\'o}gio and Isabelle Morlais and Kafatos, {Fotis C.} and Christophides, {George K.}",
year = "2009",
month = "8",
doi = "10.1371/journal.ppat.1000542",
language = "English (US)",
volume = "5",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "8",

}

TY - JOUR

T1 - Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites

AU - Meister, Stephan

AU - Agianian, Bogos

AU - Turlure, Fanny

AU - Relógio, Angela

AU - Morlais, Isabelle

AU - Kafatos, Fotis C.

AU - Christophides, George K.

PY - 2009/8

Y1 - 2009/8

N2 - 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-kB 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.

AB - 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-kB 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.

UR - http://www.scopus.com/inward/record.url?scp=70049114176&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70049114176&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.1000542

DO - 10.1371/journal.ppat.1000542

M3 - Article

C2 - 19662170

AN - SCOPUS:70049114176

VL - 5

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 8

M1 - e1000542

ER -