Dan Hultmark

The immune response in Drosophila

Our research is focused on the mechanisms of innate immunity, using Drosophila as a model system. This organism lacks lymphocytes and an acquired immune response, but has a well developed innate immune system. Studies of Drosophila have already contributed significantly to our understanding of innate immunity in humans. In addition, insect immunity is of great theoretical and practical importance in its own right, not least because insects are vectors for serious human diseases, and because insect pathogens are increasingly used to control agricultural pests.

The antibacterial response.
When infected, insects synthesize a powerful set of antibacterial proteins and peptides such as the cecropins, first discovered in the cecropia moth. They provide a rapid broad-spectrum protection against bacteria as well as fungi. Genes for many of the antibacterial peptides in Drosophila have previously been characterized in our lab. We now focus our attention on the recognition and signaling events that lead to the induction of these genes.

The cellular response.
Blood cells, called hemocytes, patrol the hemocoel in Drosophila. They phagocytize bacteria and other foreign particles, and they form capsules around parasites. They are also involved in the deposition of black melanin in the capsules and at wound sites. We are interested in the interactions between hemocytes and pathogenic organisms, and in how the encapsulation response is controlled.

On-going research
Signal transduction pathways of the immune response. Two major signaling pathways for the immune response are now relatively well established in Drosophila, both of which rely on transcription factors of the NF-kB/Rel family. One pathway mediates signals from the membrane receptor Toll and leads to activation of the transcription factor Dif. We could early demonstrate the involvement of Toll in immune responses, but most of our research has been focused on the second pathway, which is of major importance in the induction of the antimicrobial response. It involves another transcription factor, Relish, first discovered in our lab. We later showed that Relish is activated via a novel proteolytic mechanism which requires the caspase Dredd. We are now focusing on the role of these and other pathways in cellular immunity. We are particularly interested in how hemocytes are activated in response to parasites. For this purpose we use Drosophila transgenic technology and genetic screens to identify the receptors and signaling pathways involved.

Specific recognition: hemocyte surface proteins. The PGRP proteins were first discovered in moths, as blood proteins that specifically bind to bacterial peptidoglycans and that mediate the activation of phenoloxidase in response to bacteria. In collaboration with Istvan Ando's lab in Szeged we are now studying other surface markers on hemocytes such as the Nimrod proteins. They are potential receptors for the phagocytosis of bacteria.

A novel persistent virus: the Nora virus. We have discovered a virus, the Nora virus, which is produced in large quantities by some Drosophila strains, apparently without causing any obvious pathology. The Nora virus is the first member of a novel family of picorna-like viruses. We are now interested in the mechanisms that regulate the persistence of this virus.
Evolution of immunity. The selection pressures on the immune system by parasites and pathogenic or harmless microorganisms have lead to a very dynamic evolution of different families of immune-related genes. The traces of this evolution can now be studied in detail thanks to recent or on-going genome projects.

GFP-labeled blood cells (green) attack a parasitic wasp egg (black) inside a living Drosophila larva.  

Publications

Author

Title

Year sorteringsordning

Fulltext

Schmid, Martin Rudolf
Anderl, I
Vesala, L; et al.

Control of Drosophila blood cell activation via toll signaling in the fat body
PLoS ONE, 9(8): e102568-

2014

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Vanha-Aho, Leena-Maija
Kleino, Anni
Kaustio, Meri; et al.

Functional Characterization of the Infection-Inducible Peptide Edin in Drosophila melanogaster
PLoS ONE, 7(5): e37153-

2012

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Sampson, Christopher J
Valanne, Susanna
Fauvarque, Marie-Odile; et al.

The RhoGEF Zizimin-related acts in the Drosophila cellular immune response via the Rho GTPases Rac2 and Cdc42
Developmental and Comparative Immunology, 38(1): 160-168

2012

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van Mierlo, Joël T
Bronkhorst, Alfred W
Overheul, Gijs J; et al.

Convergent evolution of argonaute-2 slicer antagonism in two distinct insect RNA viruses
PLoS pathogens, 8(8): e1002872-

2012

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Ekström, Jens-Ola
Habayeb, Mazen S
Srivastava, Vaibhav; et al.

Drosophila Nora virus capsid proteins differ from those of other picorna-like viruses
Virus Research, 160(1-2): 51-58

2011

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Ulvila, Johanna
Vanha-aho, Leena-Maija
Kleino, Anni; et al.

Cofilin regulator 14-3-3zeta is an evolutionarily conserved protein required for phagocytosis and microbial resistance
Journal of Leukocyte Biology, 89(5): 649-659

2011

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Ulvila, J
Hultmark, Dan
Rämet, M

RNA silencing in the antiviral innate immune defence--role of DEAD-box RNA helicases
Scandinavian Journal of Immunology, 71(3): 146-158

2010

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Pokrzywa, Malgorzata
Dacklin, Ingrid
Vestling, Monika; et al.

Uptake of aggregating transthyretin by fat body in a drosophila model for TTR-associated amyloidosis
PloS one, 5(12): e14343-

2010

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Valanne, Susanna
Myllymäki, Henna
Kallio, Jenni; et al.

Genome-wide RNA interference in Drosophila cells identifies G protein-coupled receptor kinase 2 as a conserved regulator of NF-κB signaling
Journal of Immunology, 184(11): 6188-6198

2010

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Werren, John H
Richards, Stephen
Desjardins, Christopher A; et al.

Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.
Science, 327(5963): 343-8

2010

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Wiklund, Magda-Lena
Steinert, Stefanie
Junell, Anna; et al.

The N-terminal half of the Drosophila Rel/NF-kappaB factor Relish, REL-68, constitutively activates transcription of specific Relish target genes
Developmental and Comparative Immunology, 33(5): 690-696

2009

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Habayeb, Mazen S
Ekström, Jens-Ola
Hultmark, Dan

Nora virus persistent infections are not affected by the RNAi machinery.
PLoS ONE, 4(5): e5731-

2009

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Steiner, Håkan
Hultmark, Dan
Engström, Åke; et al.

Sequence and specificity of two antibacterial proteins involved in insect immunity. Nature 292: 246-248. 1981.
Journal of immunology (Baltimore, Md. : 1950), 182(11): 6635-7

2009

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Márkus, Róbert
Laurinyecz, Barbara
Kurucz, Eva; et al.

Sessile hemocytes as a hematopoietic compartment in Drosophila melanogaster
Proceedings of the National Academy of Sciences of the United States of America, 106(12): 4805-4809

2009

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Habayeb, Mazen
Cantera, Rafael
Casanova, Gabriela; et al.

The Drosophila Nora virus is an enteric virus, transmitted via feces
Journal of Invertebrate Pathology, 101: 29-33

2009

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Somogyi, Kálmán
Sipos, Botond
Pénzes, Zsolt; et al.

Evolution of genes and repeats in the Nimrod superfamily.
Mol Biol Evol, 25(11): 2337-47

2008

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Kleino, Anni
Myllymäki, Henna
Kallio, Jenni; et al.

Pirk is a negative regulator of the Drosophila Imd pathway.
J Immunol, 180(8): 5413-22

2008

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Richards, Stephen
Gibbs, Richard A
Weinstock, George M; et al.

The genome of the model beetle and pest Tribolium castaneum.
Nature, 452(7190): 949-55

2008

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Sackton, Timothy B
Lazzaro, Brian P
Schlenke, Todd A; et al.

Dynamic evolution of the innate immune system in Drosophila.
Nat Genet, 39(12): 1461-8

2007

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Drosophila 12 Genomes Consortium,
Hultmark, Dan

Evolution of genes and genomes on the Drosophila phylogeny.
Nature, 450(7167): 203-18

2007

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Page Editor: Dan Hultmark
2010-09-08

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Department of Molecular Biology
Umeå University
901 87 Umeå 

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6K och 6L, Sjukhusområdet, 6L-243

Tel:  +46 (0)90-7856778

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