Tissue-autonomous immune response regulates stress signalling during hypertrophy

Krautz, Robert; Khalili, Dilan; Theopold, Ulrich

doi:10.1101/787226

Cited by 4 publications

(22 citation statements)

References 97 publications

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“…S1H,I). In summary, these data show that beyond induction of antimicrobial peptides and hemocyte recruitment [46], Ras V12 -SGs display local activation of the hemostatic system. This includes structural clot components such as Tiggrin as well as enzymatic activities such as transglutaminase, followed by recruitment of phenoloxidases.…”

Section: The Immune System Targets Dysplastic Salivary Glandsmentioning

confidence: 71%

“…Fly strains and sample preparation 6 w 1118 ,Beadex MS1096 -Gal4 (Referred here as Bx: 8860/Bl), w 1118 , w 1118 ;;UAS-Ras V12 (4847/Bl), w 1118 ;;UAS-Drs (Drs-OE: overexpression [46], w 1118 ; Vkg G00454 /CyO.GFP [48], UAS-Drs-HA [49], Bx,mCD8::RFP [46] and Sgs3-GFP (5884 /Bl), (see also supplementary table S1).…”

Section: Methodsmentioning

confidence: 99%

“…Female virgins were collected for five days, crossed to the respective male on day 7. Progeny larvae were grown as described in [46]. 10-20 salivary gland pairs were fixed in 4% PFA for 20 min.…”

Section: Methodsmentioning

confidence: 99%

“…RNA extraction, cDNA synthesis and qPCR analysis were performed as described in [46]. qPCR was performed on three independent replicas targeting Rpl32, Sgs3 and Eig73Ee.…”

Section: Reverse Transcription Quantitative Pcr (Rt-qpcr)mentioning

confidence: 99%

“…We had previously found that Drs is expressed most strongly in the proximal region of Ras V12 -glands, a region which displayed fewer signs of fibrosis and looked more similar to wild type SGs. We had also managed to revert collagen IV deregulation by expressing Drs across whole glands including the strongly affected distal part [46], while expression of control GFP [29] and membrane-bound RFP [46] under the same UAS control had no such effects. Therefore, we wondered whether the fibrotic distribution of other BM components was be rescued upon forced Drs expression across whole glands.…”

Section: An Antimicrobial Peptide Reverts Bm Dysplasia Loss Of Epithmentioning

confidence: 99%

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Anti-fibrotic activity of an antimicrobial peptide in aDrosophilamodel

Khalili

Kalcher

Baumgärtner

et al. 2021

Preprint

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Fibrotic lesions accompany several pathological conditions including tumors. We show that expression of a dominant-active form of the Ras oncogene in Drosophila salivary glands (SGs) leads to redistribution of components of the basement membrane (BM) and fibrotic lesions. Similar to several types of mammalian fibrosis, the disturbed BM attracts clot components including insect transglutaminase and phenoloxidase. SG epithelial cells show reduced apico-basal polarity accompanied by a loss of secretory activity. Both the fibrotic lesions and the reduced cell polarity are alleviated by ectopic expression of the antimicrobial peptide Drosomycin (Drs), which also restores secretory activity of the SGs. In addition to ECM components, both Drs and F-actin localize to fibrotic lesions.

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Section: The Immune System Targets Dysplastic Salivary Glandsmentioning

confidence: 71%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…RNA extraction, cDNA synthesis and qPCR analysis were performed as described in [46]. qPCR was performed on three independent replicas targeting Rpl32, Sgs3 and Eig73Ee.…”

Section: Reverse Transcription Quantitative Pcr (Rt-qpcr)mentioning

confidence: 99%

Section: An Antimicrobial Peptide Reverts Bm Dysplasia Loss Of Epithmentioning

confidence: 99%

See 3 more Smart Citations

Anti-fibrotic activity of an antimicrobial peptide in aDrosophilamodel

Khalili

Kalcher

Baumgärtner

et al. 2021

Preprint

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Cecropins contribute toDrosophilahost defence against fungal and Gram-negative bacterial infection

Carboni

Hanson

Lindsay

et al. 2021

Preprint

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Cecropins are small helical secreted peptides with antimicrobial activity that are widely distributed among insects. Genes encoding cecropins are strongly induced upon infection, pointing to their role in host-defense. In Drosophila, four cecropin genes clustered in the genome (CecA1, CecA2, CecB and CecC) are expressed upon infection downstream of the Toll and Imd pathways. In this study, we generated a short deletion ΔCecA-C removing the whole cecropin locus. Using the ΔCecA-C deficiency alone or in combination with other antimicrobial peptide (AMP) mutations, we addressed the function of cecropins in the systemic immune response. ΔCecA-C flies were viable and resisted challenge with various microbes as wild-type. However, removing ΔCecA-C in flies already lacking ten other AMP genes revealed a role for cecropins in defense against Gram-negative bacteria and fungi. Measurements of pathogen loads confirm that cecropins contribute to the control of certain Gram-negative bacteria, notably Enterobacter cloacae and Providencia heimbachae. Collectively, our work provides the first genetic demonstration of a role for cecropins in insect host defense, and confirms their in vivo activity primarily against Gram-negative bacteria and fungi. Generation of a fly line (ΔAMP14) that lacks fourteen immune inducible AMPs provides a powerful tool to address the function of these immune effectors in host-pathogen interactions and beyond.

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Chitinase-like proteins promoting tumorigenesis through disruption of cell polarity via enlarged endosomal vesicles

Khalili

Kunc

Herbrich

et al. 2022

Preprint

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Chitinase-like proteins (CLPs) are associated with tissue-remodelling and inflammation but also with several disorders, including fibrosis, atherosclerosis, allergies, and cancer. However, the CLP's role in tumors is far from clear. Here, we utilize Drosophila melanogaster to investigate the function of CLPs (imaginal disc growth factors; Idgf's) in RasV12 dysplastic salivary glands (SGs). We find one of the Idgf's members, Idgf3, to be transcriptionally induced in a tissue- and cell-autonomously manner in a Drosophila hypertrophic model for early tumor progression. Induction involves non-canonical JNK-signaling via a positive feedback loop mediated by reactive oxygen species (ROS). Moreover, Idgf3 accumulates in enlarged vesicles (EnVs) that promote tumor progression by disrupting cytoskeletal organization, independent of Rab5 and Rab11. The process is mediated via Rac1 and the downstream component,Spectrin, which localizes to the EnVs. Similar to Idgf3, expression of two human members of the CLP family in Drosophila SGs aggravates tumor-related phenotypes. Our data provide new insight into a phylogenetically conserved tissue-autonomous CLP function in tumors and identify specific targets for tumor control.

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Tissue-autonomous immune response regulates stress signalling during hypertrophy

Abstract: 13 14 Postmitotic tissues are incapable of replacing damaged cells through proliferation, but need to 15 rely on buffering mechanisms to prevent tissue disintegration. By constitutively activating the 16 Ras/MAPK-pathway via Ras V12

Cited by 4 publications

References 97 publications

Anti-fibrotic activity of an antimicrobial peptide in aDrosophilamodel

Anti-fibrotic activity of an antimicrobial peptide in aDrosophilamodel

Cecropins contribute toDrosophilahost defence against fungal and Gram-negative bacterial infection

Chitinase-like proteins promoting tumorigenesis through disruption of cell polarity via enlarged endosomal vesicles

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