ArticlePLoS pathogens2014
Human IGF1 regulates midgut oxidative stress and epithelial homeostasis to balance lifespan and Plasmodium falciparum resistance in Anopheles stephensi.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Immune-reproductive cross talk in mosquitoes: molecular pathways and energy homeostasis.Parasites & vectors · 2026Review
- Blood feeding, microbiota, and layered mosquito immunity: from pathway phenotypes to vector competence.Frontiers in immunology · 2026Review
- TNF signaling mediates cellular immune function and promotes malaria parasite killing in the mosquito Anopheles gambiae.PLoS pathogens · 2025Article
- Hormones in malaria infection: influence on disease severity, host physiology, and therapeutic opportunities.Bioscience reports · 2024Review
- Evolution of innate immunity: lessons from mammalian models shaping our current view of insect immunity.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2024Review
- Coal dust nanoparticles induced pulmonary fibrosis by promoting inflammation and epithelial-mesenchymal transition via the NF-κB/NLRP3 pathway driven by IGF1/ROS-mediated AKT/GSK3β signals.Cell death discovery · 2022Article
- The effect of the sugar metabolism on Leishmania infantum promastigotes inside the gut of Lutzomyia longipalpis: A sweet relationship?PLoS neglected tropical diseases · 2022Article
- Article
- Increased insulin signaling in the Anopheles stephensi fat body regulates metabolism and enhances the host response to both bacterial challenge and Plasmodium falciparum infection.Insect biochemistry and molecular biology · 2021Article
- Review
- Mechanisms of TLR4-Mediated Autophagy and Nitroxidative Stress.Frontiers in cellular and infection microbiology · 2021Review
- Article
- The Ras/ERK signaling pathway couples antimicrobial peptides to mediate resistance to dengue virus in Aedes mosquitoes.PLoS neglected tropical diseases · 2020Article
- Midgut Mitochondrial Function as a Gatekeeper for Malaria Parasite Infection and Development in the Mosquito Host.Frontiers in cellular and infection microbiology · 2020Review
- Host serum iron modulates dengue virus acquisition by mosquitoes.Nature microbiology · 2019Article
- Anopheles aquasalis transcriptome reveals autophagic responses to Plasmodium vivax midgut invasion.Parasites & vectors · 2019Article
- Insulin-Like Peptide Signaling in Mosquitoes: The Road Behind and the Road Ahead.Frontiers in endocrinology · 2019Review
- Paraquat-Mediated Oxidative Stress inProteomes · 2018Article
- Inhibition of JNK signaling in the Asian malaria vector Anopheles stephensi extends mosquito longevity and improves resistance to Plasmodium falciparum infection.PLoS pathogens · 2018Article
- Abscisic acid induces a transient shift in signaling that enhances NF-κB-mediated parasite killing in the midgut of Anopheles stephensi without reducing lifespan or fecundity.Parasites & vectors · 2017Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Insulin and insulin-like growth factor signaling (IIS) regulates cell death, repair, autophagy, and renewal in response to stress, damage, and pathogen challenge. Therefore, IIS is fundamental to lifespan and disease resistance. Previously, we showed that insulin-like growth factor 1 (IGF1) within a physiologically relevant range (0.013-0.13 µM) in human blood reduced development of the human parasite Plasmodium falciparum in the Indian malaria mosquito Anopheles stephensi. Low IGF1 (0.013 µM) induced FOXO and p70S6K activation in the midgut and extended mosquito lifespan, whereas high IGF1 (0.13 µM) did not. In this study the physiological effects of low and high IGF1 were examined in detail to infer mechanisms for their dichotomous effects on mosquito resistance and lifespan. Following ingestion, low IGF1 induced phosphorylation of midgut c-Jun-N-terminal kinase (JNK), a critical regulator of epithelial homeostasis, but high IGF1 did not. Low and high IGF1 induced midgut mitochondrial reactive oxygen species (ROS) synthesis and nitric oxide (NO) synthase gene expression, responses which were necessary and sufficient to mediate IGF1 inhibition of P. falciparum development. However, increased ROS and apoptosis-associated caspase-3 activity returned to baseline levels following low IGF1 treatment, but were sustained with high IGF1 treatment and accompanied by aberrant expression of biomarkers for mitophagy, stem cell division and proliferation. Low IGF1-induced ROS are likely moderated by JNK-induced epithelial cytoprotection as well as p70S6K-mediated growth and inhibition of apoptosis over the lifetime of A. stephensi to facilitate midgut homeostasis and enhanced survivorship. Hence, mitochondrial integrity and homeostasis in the midgut, a key signaling center for IIS, can be targeted to coordinately optimize mosquito fitness and anti-pathogen resistance for improved control strategies for malaria and other vector-borne diseases.
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