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- Ekengren, Sophia, et al.
(författare)
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A humoral stress response in Drosophila.
- 2001
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Ingår i: Curr Biol. - 0960-9822. ; 11:9, s. 714-8
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Tidskriftsartikel (refereegranskat)abstract
- The ability to react to unfavorable environmental changes is crucial for survival and reproduction, and several adaptive responses to stress have been conserved during evolution [1-3]. Specific immune and heat shock responses mediate the elimination of invading pathogens and of damaged proteins or cells [4-6]. Furthermore, MAP kinases and other signaling factors mediate cellular responses to a very broad range of environmental insults [7-9]. Here we describe a novel systemic response to stress in Drosophila. The Turandot A (TotA) gene encodes a humoral factor, which is secreted from the fat body and accumulates in the body fluids. TotA is strongly induced upon bacterial challenge, as well as by other types of stress such as high temperature, mechanical pressure, dehydration, UV irradiation, and oxidative agents. It is also upregulated during metamorphosis and at high age. Strikingly, flies that overexpress TotA show prolonged survival and retain normal activity at otherwise lethal temperatures. Although TotA is only induced by severe stress, it responds to a much wider range of stimuli than heat shock genes such as hsp70 or immune genes such as Cecropin A1.
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| 4. |
- Gelius, Eva, et al.
(författare)
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A mammalian peptidoglycan recognition protein with N-acetylmuramoyl-L-alanine amidase activity
- 2003
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - 0006-291X .- 1090-2104. ; 306:4, s. 988-994
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Tidskriftsartikel (refereegranskat)abstract
- The family of peptidoglycan recognition proteins (PGRPs) is conserved from insects to mammals. Recently, Drosophila PGRP-SC1B was demonstrated to be an N-acetylmuramoyl- -alanine amidase (NAMLAA), an enzyme that cleaves the lactylamide bond between muramic acid and the peptide chain in peptidoglycan (PGN). We now show an M.mPGRP-L mRNA to be expressed in the liver. The recombinant M.mPGRP-L protein has NAMLAA activity and degrades PGN from both Escherichia coli and Staphylococcus aureus; however, the Gram-positive PGN was a better substrate after lysozyme treatment. The activity of M.mPGRP-L was further analysed using Bordetella pertussis tracheal toxin as a substrate. Cleavage products were separated on HPLC and identified using mass spectrometry. From these results we conclude that M.mPGRP-L has activity and other properties identifying it as the NAMLAA protein present in mammalian sera.
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- Karlsson, Jenny, et al.
(författare)
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Growing bacteria shed elicitors of Drosophila humoral immunity.
- 2012
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Ingår i: Journal of innate immunity. - : S. Karger AG. - 1662-8128 .- 1662-811X. ; 4:1, s. 111-116
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Tidskriftsartikel (refereegranskat)abstract
- It has been much debated how the Drosophila immune system can recognize bacterial peptidoglycan that is often hidden. We show that bacteria separated from Drosophila S2 cells by a semipermeable membrane can upregulate the Imd pathway. Supernatants from exponentially growing but not from stationary-phase bacterial cultures induce antimicrobial peptides. It is also made likely that the shed elicitors are of peptidoglycan nature.
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| 8. |
- Karlsson, Jenny, 1976-, et al.
(författare)
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Growing bacteria shed elicitors of Drosophila humoral immunity
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Karlsson, Jenny, 1976-
(författare)
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Peptidoglycan regulation of Drosophila immunity
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 10. |
- Lindberg, Bo G., et al.
(författare)
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Medium from gamma-irradiated Escherichia coli bacteria stimulates a unique immune response in Drosophila cells
- 2014
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Ingår i: Developmental and Comparative Immunology. - : Elsevier BV. - 0145-305X .- 1879-0089. ; 46:2, s. 392-400
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that gamma-irradiated, non-dividing bacteria can elicit potent immune responses in mammals. Compared to traditional heat or chemical inactivation of microbes, gamma -irradiation likely preserves metabolic activity and antigenic features to a larger extent. We have previously shown that antimicrobial peptides are induced in Drosophila by peptidoglycan fragments secreted into the medium of exponentially growing bacterial cultures. In this study, we gamma-irradiated Escherichia coil cells at a dose that halted cell division. The temporal synthesis and release of peptidoglycan fragments were followed as well as the potential of bacterial supernatants to induce immune responses in Drosophila S2 cells. We demonstrate that peptidoglycan synthesis continues for several days post irradiation and that monomeric peptidoglycan is shed into the medium. Whole transcriptome analysis revealed a strong immune response against the bacterial medium. The response to medium taken directly post irradiation shows a large overlap to that of peptidoglycan. Medium from prolonged bacterial incubation does, however, stimulate a selective set of immune genes. A shift towards a stress response was instead observed with a striking induction of several heat shock proteins. Our findings suggest that gamma-irradiated bacteria release elicitors that stimulate a novel response in Drosophila.
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