The Role of PGRP Proteins in Innate Immunity Pathways in the Malaria Vector Anopheles gambiae
type: CreativeWork
description: Innate immunity is the first line of defense against invading microorganisms and provides clues to adaptive immunity for the development of memory for subsequent infections. Insects, similar to other invertebrates, do not have adaptive immunity and thus rely on their innate immune system to combat infections. We have analyzed the role of the peptidoglycan (PGN) receptor protein (PGRP) family and other components of innate immune signaling pathways in the immune defense of the mosquito Anopheles gambiae, the main vector of human malaria in sub-Saharan Africa. The PGRP gene family consists of seven genes with ten PGRP domains. We have shown that from all PGRP genes only PGRPLC has a role in the resistance to bacterial infections of both Gram types. In our experiments we have used the Gram-positive bacterium Staphylococcus aureus and the Gram-negative bacterium Escherichia coli. The PGRPLC gene encodes at least three isoforms that derive from infection-driven alternative splicing of a pool of immature transcripts. Each isoform contains a different PGRP domain, encoded by three exons that all contribute equally to the PGN binding pocket. Structural modeling of the PGRPLC isoforms revealed a potential for all isoforms to bind both types of PGN, the Lys-type, which is mostly found in Gram-positive bacteria and the DAP-type, mostly found in Gram-negative bacteria. The isoform PGRPLC3 seems to be the most important in the defense against both bacteria species, although PGRPLC1 also has a crucial role in the defense against S. aureus. Bacterial defense is mediated by the NF-κB transcription factor REL2, which is the ortholog of the Drosophila Relish. The REL2 gene also encodes two protein isoforms: REL2-S, which only has the NF-κB domain, and REL2-F, which carries an I-κB inhibitory domain and a death domain in addition. REL2-F functions together with the receptor adaptor protein IMD to deal with S. aureus infections, whereas REL2-S has a role in the defense against E. coli.…
abstract: Innate immunity is the first line of defense against invading microorganisms and provides clues to adaptive immunity for the development of memory for subsequent infections. Insects, similar to other invertebrates, do not have adaptive immunity and thus rely on their innate immune system to combat infections. We have analyzed the role of the peptidoglycan (PGN) receptor protein (PGRP) family and other components of innate immune signaling pathways in the immune defense of the mosquito Anopheles gambiae, the main vector of human malaria in sub-Saharan Africa. The PGRP gene family consists of seven genes with ten PGRP domains. We have shown that from all PGRP genes only PGRPLC has a role in the resistance to bacterial infections of both Gram types. In our experiments we have used the Gram-positive bacterium Staphylococcus aureus and the Gram-negative bacterium Escherichia coli. The PGRPLC gene encodes at least three isoforms that derive from infection-driven alternative splicing of a pool of immature transcripts. Each isoform contains a different PGRP domain, encoded by three exons that all contribute equally to the PGN binding pocket. Structural modeling of the PGRPLC isoforms revealed a potential for all isoforms to bind both types of PGN, the Lys-type, which is mostly found in Gram-positive bacteria and the DAP-type, mostly found in Gram-negative bacteria. The isoform PGRPLC3 seems to be the most important in the defense against both bacteria species, although PGRPLC1 also has a crucial role in the defense against S. aureus. Bacterial defense is mediated by the NF-κB transcription factor REL2, which is the ortholog of the Drosophila Relish. The REL2 gene also encodes two protein isoforms: REL2-S, which only has the NF-κB domain, and REL2-F, which carries an I-κB inhibitory domain and a death domain in addition. REL2-F functions together with the receptor adaptor protein IMD to deal with S. aureus infections, whereas REL2-S has a role in the defense against E. coli.…
author: Meister, Stephan
date published: 2006-10-19
date modified: 2026-07-24T02:30:27Z
provider: Universität Heidelberg
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Universität Heidelberg