A mosquito juvenile hormone binding protein (mJHBP) regulates the activation of innate immune defenses and hemocyte development

Autoři: Il Hwan Kim aff001;  Julio César Castillo aff001;  Azadeh Aryan aff002;  Inés Martin-Martin aff001;  Marcela Nouzova aff003;  Fernando G. Noriega aff003;  Ana Beatriz F. Barletta aff001;  Eric Calvo aff001;  Zachary N. Adelman aff002;  José M. C. Ribeiro aff001;  John F. Andersen aff001
Působiště autorů: NIH/NIAID Laboratory of Malaria and Vector Research, 12735 Twinbrook Parkway, Rockville, MD, United States of America aff001;  Department of Entomology and AgriLife Research, Texas A&M University, College Station, United States of America aff002;  Department of Biological Sciences and Biomolecular Science Institute, Florida International University, Miami, United States of America aff003;  Institute of Parasitology, Biology Centre CAS, Ceske Budejovice, Czech Republic aff004
Vyšlo v časopise: A mosquito juvenile hormone binding protein (mJHBP) regulates the activation of innate immune defenses and hemocyte development. PLoS Pathog 16(1): e32767. doi:10.1371/journal.ppat.1008288
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008288


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.

Klíčová slova:

Bacterial diseases – Escherichia coli infections – Fats – Granulocytes – Hemocytes – Immune response – Larvae – Mosquitoes


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