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Growing bacteria shed elicitors of Drosophila humoral immunity
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology. (Håkan Steiner)
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology. (Håkan Steiner)
(Håkan Steiner)
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology. (Håkan Steiner)
(English)Article in journal (Refereed) Submitted
Abstract [en]

Peptidoglycan (PGN) is a well-characterized cell wall component from bacteria that is recognized by Peptidoglycan Recognition Receptors (PGRPs) in the Drosophila immune system. It has long been a forum of debate how the immune system is able to recognize this elicitor since the PGN is hidden by the outer membrane in gram-negative bacteria and by teichoic acids in gram-positive bacteria. We show here that bacteria separated from Drosophila S2 cells by a semi permeable membrane are able to up-regulate the Imd pathway. Studies with supernatants from exponentially growning bacterial cultures show that bacteria shed elicitors in sufficient amounts to potentially induce the Imd pathway. However, when employing supernatants from bacteria in stationary phase, no stimulatory effect of the Imd pathway was detected. The elicitor effect was much reduced when the supernatans was treated with the N-acetylmuramoyl-Lalanine amidase M.mPGRP-L, which is a known scavenger of PGN. Our studies therefore indicate that bacteria in growth phase shed elicitors of PGN nature that can induce a humoral immune response in Drosophila S2 cells.

URN: urn:nbn:se:su:diva-29783OAI: diva2:235348
Available from: 2009-09-15 Created: 2009-09-14 Last updated: 2010-01-11Bibliographically approved
In thesis
1. Peptidoglycan regulation of Drosophila immunity
Open this publication in new window or tab >>Peptidoglycan regulation of Drosophila immunity
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Innate immunity is an ancient defense system that distinguishes between self and non self and is present in both vertebrates and invertebrates. Peptidoglycan (PGN), a cell wall component shared by both gram-negative and gram-positive bacteria, is the major recognition molecule for the detection of bacteria in Drosophila. Peptidoglycan Recognition Proteins (PGRPs) are conserved from insect to mammals and bind PGN with high affinity. In Drosophila, distinct PGRPs provide essential signals upstream of the Toll and Imd pathways. This thesis concerns the recognition of PGN by PGRPs and the expression of antibacterial peptides from the Imd pathway.

The PGRP-LC locus encodes three splice forms, a, x, and y. PGRP-LCx and PGRP-LCa form heterodimers in the presence of monomeric PGN. We propose a model for activation of Imd where PGRP-LCx binds to monomeric PGN leading to dimerization with PGRP-LCa and activation of the Imd pathway. With polymeric PGN, PGRP-LCx dimers activate the Imd pathway.

Drosophila PGRP-SC1B has amidase activity and cleaves the PGN lactamyl bond between the glycan strand and the peptide. The digested material is less immunogenic than intact PGN or PGN digested by egg white lysozyme. We suggest PGRP-SC1B to be a scavenger of immunogenic PGN. Amino acid sequence homology predicts six of the Drosophila PGRPs as well as two vertebrate PGRPs to be amidases. Murine PGRP-L is expressed in the liver and was shown to have PGN degrading activity. We found that an earlier purified human serum amidase is in fact identical to PGRP-L.

Although PGN is a potential trigger of the insect immune system, the actual detection of PGN in vivo poses problems. In gram-negative bacteria, PGN is covered by an outer membrane. Using a cell line approach we demonstrate that bacteria can be recognized by the Imd pathway without the need of phagocytosis or contact between bacteria and cells. Instead growing bacteria release immune eliciting fragments of PGN nature.

Place, publisher, year, edition, pages
Stockholm: Department of Genetics, Microbiology and Toxicology, Stockholm University, 2009. 50 p.
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Genetics
urn:nbn:se:su:diva-29828 (URN)978-91-7155-938-8 (ISBN)
Public defence
2009-10-23, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Submitted.Available from: 2009-10-01 Created: 2009-09-15 Last updated: 2009-09-17Bibliographically approved

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Karlsson, JennyOldenvi, SandraSteiner, Håkan
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