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A mosquito juvenile hormone binding protein (mJHBP) regulates the activation of innate immune defenses and hemocyte development
IH. Kim, JC. Castillo, A. Aryan, I. Martin-Martin, M. Nouzova, FG. Noriega, ABF. Barletta, E. Calvo, ZN. Adelman, JMC. Ribeiro, JF. Andersen,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural
Grantová podpora
R01 AI099483
NIAID NIH HHS - United States
R01 AI045545
NIAID NIH HHS - United States
NLK
Directory of Open Access Journals
od 2005
Free Medical Journals
od 2005
Public Library of Science (PLoS)
od 2005
PubMed Central
od 2005
Europe PubMed Central
od 2005
ProQuest Central
od 2005-09-01
Open Access Digital Library
od 2005-01-01
Open Access Digital Library
od 2005-01-01
Open Access Digital Library
od 2005-09-01
Medline Complete (EBSCOhost)
od 2005-09-01
Health & Medicine (ProQuest)
od 2005-09-01
ROAD: Directory of Open Access Scholarly Resources
od 2005
- MeSH
- Aedes genetika růst a vývoj imunologie mikrobiologie MeSH
- hemocyty imunologie mikrobiologie MeSH
- hmyzí proteiny genetika imunologie MeSH
- juvenilní hormony imunologie MeSH
- larva genetika růst a vývoj imunologie mikrobiologie MeSH
- přirozená imunita MeSH
- Serratia marcescens fyziologie MeSH
- transportní proteiny genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
Insects rely on the innate immune system for defense against pathogens, some aspects of which are under hormonal control. Here we provide direct experimental evidence showing that the juvenile hormone-binding protein (mJHBP) of Aedes aegypti is required for the regulation of innate immune responses and the development of mosquito blood cells (hemocytes). Using an mJHBP-deficient mosquito line generated by means of CRISPR-Cas9 gene editing technology we uncovered a mutant phenotype characterized by immunosuppression at the humoral and cellular levels, which profoundly affected susceptibility to bacterial infection. Bacteria-challenged mosquitoes exhibited significantly higher levels of septicemia and mortality relative to the wild type (WT) strain, delayed expression of antimicrobial peptides (AMPs), severe developmental dysregulation of embryonic and larval hemocytes (reduction in the total number of hemocytes) and increased differentiation of the granulocyte lineage. Interestingly, injection of recombinant wild type mJHBP protein into adult females three-days before infection was sufficient to restore normal immune function. Similarly, injection of mJHBP into fourth-instar larvae fully restored normal larval/pupal hemocyte populations in emerging adults. More importantly, the recovery of normal immuno-activation and hemocyte development requires the capability of mJHBP to bind JH III. These results strongly suggest that JH III functions in mosquito immunity and hemocyte development in a manner that is perhaps independent of canonical JH signaling, given the lack of developmental and reproductive abnormalities. Because of the prominent role of hemocytes as regulators of mosquito immunity, this novel discovery may have broader implications for the understanding of vector endocrinology, hemocyte development, vector competence and disease transmission.
Citace poskytuje Crossref.org
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- $a Insects rely on the innate immune system for defense against pathogens, some aspects of which are under hormonal control. Here we provide direct experimental evidence showing that the juvenile hormone-binding protein (mJHBP) of Aedes aegypti is required for the regulation of innate immune responses and the development of mosquito blood cells (hemocytes). Using an mJHBP-deficient mosquito line generated by means of CRISPR-Cas9 gene editing technology we uncovered a mutant phenotype characterized by immunosuppression at the humoral and cellular levels, which profoundly affected susceptibility to bacterial infection. Bacteria-challenged mosquitoes exhibited significantly higher levels of septicemia and mortality relative to the wild type (WT) strain, delayed expression of antimicrobial peptides (AMPs), severe developmental dysregulation of embryonic and larval hemocytes (reduction in the total number of hemocytes) and increased differentiation of the granulocyte lineage. Interestingly, injection of recombinant wild type mJHBP protein into adult females three-days before infection was sufficient to restore normal immune function. Similarly, injection of mJHBP into fourth-instar larvae fully restored normal larval/pupal hemocyte populations in emerging adults. More importantly, the recovery of normal immuno-activation and hemocyte development requires the capability of mJHBP to bind JH III. These results strongly suggest that JH III functions in mosquito immunity and hemocyte development in a manner that is perhaps independent of canonical JH signaling, given the lack of developmental and reproductive abnormalities. Because of the prominent role of hemocytes as regulators of mosquito immunity, this novel discovery may have broader implications for the understanding of vector endocrinology, hemocyte development, vector competence and disease transmission.
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