Anti-Tumor Effect of Turandot Proteins Induced via the JAK/STAT Pathway in the mxc Hematopoietic Tumor Mutant in Drosophila

Kinoshita, Yuriko; Shiratsuchi, Naoka; Araki, Mayo; Inoué, Yoshihiro

doi:10.3390/cells12162047

Cited by 2 publications

(1 citation statement)

References 60 publications

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“…Tep1 and Tep2 , which are regulated by the JAK-STAT and Toll pathways ( 32 ), also increased in expression. Similarly, IBIN , which is regulated by the Toll and IMD pathways ( 33 ), was upregulated, as was TotC , which is regulated by the JAK-STAT pathway ( 34 ). Together these results indicate that the JAK-STAT and Toll pathways, which play a key role in the immune response to parasitoid wasps, are upregulated by wasp extract.…”

Section: Discussionmentioning

confidence: 99%

Activation of immune defences against parasitoid wasps does not underlie the cost of infection

Leitão,

Geldman,

Jiggins

2023

Front. Immunol.

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Parasites reduce the fitness of their hosts, and different causes of this damage have fundamentally different consequences for the evolution of immune defences. Damage to the host may result from the parasite directly harming its host, often due to the production of virulence factors that manipulate host physiology. Alternatively, the host may be harmed by the activation of its own immune defences, as these can be energetically demanding or cause self-harm. A well-studied model of the cost of infection is Drosophila melanogaster and its common natural enemy, parasitoid wasps. Infected Drosophila larvae rely on humoral and cellular immune mechanisms to form a capsule around the parasitoid egg and kill it. Infection results in a developmental delay and reduced adult body size. To disentangle the effects of virulence factors and immune defences on these costs, we artificially activated anti-parasitoid immune defences in the absence of virulence factors. Despite immune activation triggering extensive differentiation and proliferation of immune cells together with hyperglycaemia, it did not result in a developmental delay or reduced body size. We conclude that the costs of infection do not result from these aspects of the immune response and may instead result from the parasite directly damaging the host.

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Section: Discussionmentioning

confidence: 99%

Activation of immune defences against parasitoid wasps does not underlie the cost of infection

Leitão,

Geldman,

Jiggins

2023

Front. Immunol.

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Macrophage-like Blood Cells Are Involved in Inter-Tissue Communication to Activate JAK/STAT Signaling, Inducing Antitumor Turandot Proteins in Drosophila Fat Body via the TNF-JNK Pathway

Kinoshita,

Nomura

et al. 2024

IJMS

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Turandot (Tot) family proteins, which are induced via the JAK/STAT pathway after infection, also suppress lymph gland tumors in Drosophila mxcmbn1 mutant larvae. We investigated the potential role of hemocytes in Tot induction in tumor-bearing mutants via immunostaining and RNAi experiments. Normal hemocytes transplanted into mutant larvae were recruited to the tumor and fat body (FB), suggesting that these cells transmit tumor-related information. The transplanted hemocytes ectopically expressed Unpaired3 (Upd3), which is necessary for the activation of JAK/STAT. Eiger, a Drosophila tumor necrosis factor (TNF) ortholog, was highly expressed in tumors. Depletion of the Eiger receptor in hemocytes reduced Tot levels and eventually enhanced tumor growth. The c-Jun N-terminal kinase (JNK) pathway, acting downstream of the receptor, was also activated in the hemocytes of mutants. Downregulation of the JNK pathway in hemocytes inhibited Tot induction, leading to enhanced tumor growth. These results suggest that upd3 expression in hemocytes depends on the Eiger–JNK pathway. We propose that after Eiger activates the JNK pathway in hemocytes present on the tumor, cells expressing Upd3 are recruited to the FB. Upd3 then activates JAK/STAT to induce the expression of antitumor proteins. This study highlights the intricate communication between tissues via blood cells during tumor suppression.

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Anti-Tumor Effect of Turandot Proteins Induced via the JAK/STAT Pathway in the mxc Hematopoietic Tumor Mutant in Drosophila

Cited by 2 publications

References 60 publications

Activation of immune defences against parasitoid wasps does not underlie the cost of infection

Activation of immune defences against parasitoid wasps does not underlie the cost of infection

Macrophage-like Blood Cells Are Involved in Inter-Tissue Communication to Activate JAK/STAT Signaling, Inducing Antitumor Turandot Proteins in Drosophila Fat Body via the TNF-JNK Pathway

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