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JAK/STAT signaling in Drosophila muscles controls the cellular immune response against parasitoid infection
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
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2015 (English)In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 16, no 12, 1664-1672 p.Article in journal (Refereed) PublishedText
Abstract [en]

The role of JAK/STAT signaling in the cellular immune response of Drosophila is not well understood. Here, we show that parasitoid wasp infection activates JAK/STAT signaling in somatic muscles of the Drosophila larva, triggered by secretion of the cytokines Upd2 and Upd3 from circulating hemocytes. Deletion of upd2 or upd3, but not the related os (upd1) gene, reduced the cellular immune response, and suppression of the JAK/STAT pathway in muscle cells reduced the encapsulation of wasp eggs and the number of circulating lamellocyte effector cells. These results suggest that JAK/STAT signaling in muscles participates in a systemic immune defense against wasp infection.

Place, publisher, year, edition, pages
2015. Vol. 16, no 12, 1664-1672 p.
Keyword [en]
Drosophila, innate immunity, JAK/STAT signaling, muscles
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:umu:diva-116103DOI: 10.15252/embr.201540277ISI: 000368237100012PubMedID: 26412855OAI: oai:DiVA.org:umu-116103DiVA: diva2:901508
Available from: 2016-02-08 Created: 2016-02-08 Last updated: 2016-09-20Bibliographically approved
In thesis
1. Drosophila skeletal muscles regulate the cellular immune response against wasp infection
Open this publication in new window or tab >>Drosophila skeletal muscles regulate the cellular immune response against wasp infection
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Drosophila melanogaster is widely used as a model organism to study the innate immune system because it lacks an adaptive immune response that could mask its innate immune response. The innate immune response of Drosophila primarily consists of humoral and cellular immune responses. The humoral immune response ismediated by antimicrobial peptides, and is induced by bacterial and fungal infections. The cellular immune response is mediated by blood cells (hemocytes), and is induced by bacterial and wasp infection. While the humoral immune response of Drosophila has been studied extensively, the cellular immune response is less well understood.

In this work, I investigated the communication between different signaling pathways and tissues in Drosophila during infection by the parasitic wasp Leptopilina boulardi. I find that JAK/STAT signaling is strongly activated by wasp infection, in both hemocytes and (unexpectedly) larval skeletal muscles. This activation is mediated by the cytokines Upd2 and Upd3, which are secreted from circulating hemocytes. Deletion of upd2 or/and upd3 weakens the wasp-induced activation of JAK/STAT signaling in skeletal muscles and the cellular immune response to wasp infection, leading to reduced encapsulation of wasp eggs and a decrease in the number of circulating lamelloyctes. The suppression of JAK/STAT signaling also significantly weakens the cellular immune response in skeletal muscles, but not in fat bodies and hemocytes. However, the activation of this signaling in skeletal muscles has no obvious effect on the cellular immune response. Together, these results suggest that rather than being uninvolved bystanders, Drosophila skeletal musclesactively participate in cellular immune responses against wasp infection.

To answer how Drosophila larval muscles participate cellular immune response, I min-screened the effects of several immune related signaling pathways in the muscles and the fat body on the cellular immune response. Interestingly, the cellular immune response was only significantly compromised by the suppression ofinsulin signaling in skeletal muscles, in a way that was veryreminiscent of the phenotypes induced by suppressing JAK/STAT signaling in muscles. While wasp infection activates JAK/STAT signaling in muscles, it has the opposite effect on insulin signaling. In addition, I find that insulin signaling in skeletal muscles can positively regulate JAK/STAT signaling. On the other hand, suppression of JAK/STAT signaling in muscles reduces insulin signaling locally in muscles and systemically in the fat body. Suppression of either insulin or JAK/STAT signaling in muscles leads to reductions in glycogen storage in muscles, the trehalose concentration in the hemolymph, and the frequency of feeding behavior. All these results indicate that JAK/STAT and insulin signaling in Drosophila skeletal muscles regulate cellular immune responses via their effects on carbohydrate metabolism. Our findings shed new light on the interactions between diabetes, metabolism, the immune system, and tissue communication.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2016. 43 p.
Series
Doctoral thesis / Umeå University, Department of Molecular Biology, 1818Umeå University medical dissertations, ISSN 0346-6612
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-125842 (URN)978-91-7601-508-7 (ISBN)
Public defence
2016-10-11, hörsal E04, NUS 6A–L Biomedicinhuset, Byggnad 6E,, Umeå, 09:00 (English)
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Available from: 2016-09-20 Created: 2016-09-20 Last updated: 2016-09-21Bibliographically approved

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Yang, HairuKronhamn, JesperEkstrom, Jens-OlaKorkut, Gul GizemHultmark, Dan
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