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
Souhrn
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
Zdroje
1. Bartholomay LC, Michel K. Mosquito Immunobiology: The Intersection of Vector Health and Vector Competence. Annu Rev Entomol. 2018;63:145–67. Epub 2018/01/13. doi: 10.1146/annurev-ento-010715-023530 29324042.
2. Rus F, Flatt T, Tong M, Aggarwal K, Okuda K, Kleino A, et al. Ecdysone triggered PGRP-LC expression controls Drosophila innate immunity. EMBO J. 2013;32(11):1626–38. Epub 2013/05/09. doi: 10.1038/emboj.2013.100 23652443; PubMed Central PMCID: PMC3671248.
3. Zhang Z, Palli SR. Identification of a cis-regulatory element required for 20-hydroxyecdysone enhancement of antimicrobial peptide gene expression in Drosophila melanogaster. Insect Mol Biol. 2009;18(5):595–605. Epub 2009/09/17. doi: 10.1111/j.1365-2583.2009.00901.x 19754738.
4. Regan JC, Brandao AS, Leitao AB, Mantas Dias AR, Sucena E, Jacinto A, et al. Steroid hormone signaling is essential to regulate innate immune cells and fight bacterial infection in Drosophila. PLoS Pathog. 2013;9(10):e1003720. Epub 2013/11/10. doi: 10.1371/journal.ppat.1003720 24204269; PubMed Central PMCID: PMC3812043.
5. Upton LM, Povelones M, Christophides GK. Anopheles gambiae blood feeding initiates an anticipatory defense response to Plasmodium berghei. J Innate Immun. 2015;7(1):74–86. Epub 2014/09/24. doi: 10.1159/000365331 25247883; PubMed Central PMCID: PMC4564949.
6. Werling K, Shaw WR, Itoe MA, Westervelt KA, Marcenac P, Paton DG, et al. Steroid Hormone Function Controls Non-competitive Plasmodium Development in Anopheles. Cell. 2019;177(2):315–25 e14. Epub 2019/04/02. doi: 10.1016/j.cell.2019.02.036 30929905; PubMed Central PMCID: PMC6450776.
7. Ahmed A, Martin D, Manetti AG, Han SJ, Lee WJ, Mathiopoulos KD, et al. Genomic structure and ecdysone regulation of the prophenoloxidase 1 gene in the malaria vector Anopheles gambiae. Proc Natl Acad Sci U S A. 1999;96(26):14795–800. Epub 1999/12/28. doi: 10.1073/pnas.96.26.14795 10611292; PubMed Central PMCID: PMC24727.
8. Flatt T, Heyland A, Rus F, Porpiglia E, Sherlock C, Yamamoto R, et al. Hormonal regulation of the humoral innate immune response in Drosophila melanogaster. J Exp Biol. 2008;211(Pt 16):2712–24. Epub 2008/08/12. doi: 10.1242/jeb.014878 18689425; PubMed Central PMCID: PMC2522372.
9. Kim IH, Pham V, Jablonka W, Goodman WG, Ribeiro JMC, Andersen JF. A mosquito hemolymph odorant-binding protein family member specifically binds juvenile hormone. J Biol Chem. 2017;292(37):15329–39. Epub 2017/07/29. doi: 10.1074/jbc.M117.802009 28751377; PubMed Central PMCID: PMC5602393.
10. Alvarenga PH, Francischetti IM, Calvo E, Sa-Nunes A, Ribeiro JM, Andersen JF. The function and three-dimensional structure of a thromboxane A2/cysteinyl leukotriene-binding protein from the saliva of a mosquito vector of the malaria parasite. PLoS Biol. 2010;8(11):e1000547. Epub 2010/12/15. doi: 10.1371/journal.pbio.1000547 21152418; PubMed Central PMCID: PMC2994686.
11. Smykal V, Raikhel AS. Nutritional Control of Insect Reproduction. Curr Opin Insect Sci. 2015;11:31–8. Epub 2015/12/09. doi: 10.1016/j.cois.2015.08.003 26644995; PubMed Central PMCID: PMC4669899.
12. Hernandez-Martinez S, Rivera-Perez C, Nouzova M, Noriega FG. Coordinated changes in JH biosynthesis and JH hemolymph titers in Aedes aegypti mosquitoes. J Insect Physiol. 2015;72:22–7. Epub 2014/12/03. doi: 10.1016/j.jinsphys.2014.11.003 25445664; PubMed Central PMCID: PMC4333059.
13. Das D, Aradhya R, Ashoka D, Inamdar M. Macromolecular uptake in Drosophila pericardial cells requires rudhira function. Exp Cell Res. 2008;314(8):1804–10. Epub 2008/03/22. doi: 10.1016/j.yexcr.2008.02.009 18355807.
14. Barletta ABF, Alves LR, Silva MCLN, Sim S, Dimopoulos G, Liechocki S, et al. Emerging role of lipid droplets in Aedes aegypti immune response against bacteria and Dengue virus. Sci Rep-Uk. 2016;6. ARTN 19928 doi: 10.1038/srep19928 WOS:000370340900001. 26887863
15. Bradburn MJ, Clark TG, Love SB, Altman DG. Survival analysis part II: multivariate data analysis—an introduction to concepts and methods. Br J Cancer. 2003;89(3):431–6. Epub 2003/07/31. doi: 10.1038/sj.bjc.6601119 12888808; PubMed Central PMCID: PMC2394368.
16. Castillo J, Brown MR, Strand MR. Blood feeding and insulin-like peptide 3 stimulate proliferation of hemocytes in the mosquito Aedes aegypti. PLoS Pathog. 2011;7(10):e1002274. Epub 2011/10/15. doi: 10.1371/journal.ppat.1002274 PubMed Central PMCID: PMC3188524. 21998579
17. Castillo JC, Ferreira ABB, Trisnadi N, Barillas-Mury C. Activation of mosquito complement antiplasmodial response requires cellular immunity. Sci Immunol. 2017;2(7). Epub 2017/07/25. doi: 10.1126/sciimmunol.aal1505 28736767; PubMed Central PMCID: PMC5520810.
18. Hillyer JF, Schmidt SL, Christensen BM. Rapid phagocytosis and melanization of bacteria and Plasmodium sporozoites by hemocytes of the mosquito Aedes aegypti. J Parasitol. 2003;89(1):62–9. Epub 2003/03/28. doi: 10.1645/0022-3395(2003)089[0062:RPAMOB]2.0.CO;2 12659304.
19. Hillyer JF, Schmidt SL, Christensen BM. The antibacterial innate immune response by the mosquito Aedes aegypti is mediated by hemocytes and independent of Gram type and pathogenicity. Microbes Infect. 2004;6(5):448–59. Epub 2004/04/28. doi: 10.1016/j.micinf.2004.01.005 15109959.
20. Rodrigues J, Brayner FA, Alves LC, Dixit R, Barillas-Mury C. Hemocyte differentiation mediates innate immune memory in Anopheles gambiae mosquitoes. Science. 2010;329(5997):1353–5. Epub 2010/09/11. doi: 10.1126/science.1190689 20829487; PubMed Central PMCID: PMC3510677.
21. Roy S, Saha TT, Zou Z, Raikhel AS. Regulatory Pathways Controlling Female Insect Reproduction. Annu Rev Entomol. 2018;63:489–511. Epub 2017/10/24. doi: 10.1146/annurev-ento-020117-043258 29058980.
22. Zou Z, Saha TT, Roy S, Shin SW, Backman TW, Girke T, et al. Juvenile hormone and its receptor, methoprene-tolerant, control the dynamics of mosquito gene expression. Proc Natl Acad Sci U S A. 2013;110(24):E2173–81. Epub 2013/05/02. doi: 10.1073/pnas.1305293110 23633570; PubMed Central PMCID: PMC3683779.
23. Kawaguchi R, Yu J, Honda J, Hu J, Whitelegge J, Ping P, et al. A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. Science. 2007;315(5813):820–5. Epub 2007/01/27. doi: 10.1126/science.1136244 17255476.
24. Benoit JB, Vigneron A, Broderick NA, Wu Y, Sun JS, Carlson JR, et al. Symbiont-induced odorant binding proteins mediate insect host hematopoiesis. Elife. 2017;6. Epub 2017/01/13. doi: 10.7554/eLife.19535 28079523; PubMed Central PMCID: PMC5231409.
25. Evans CJ, Hartenstein V, Banerjee U. Thicker than blood: conserved mechanisms in Drosophila and vertebrate hematopoiesis. Dev Cell. 2003;5(5):673–90. Epub 2003/11/07. doi: 10.1016/s1534-5807(03)00335-6 14602069.
26. Hartenstein V. Blood cells and blood cell development in the animal kingdom. Annu Rev Cell Dev Biol. 2006;22:677–712. Epub 2006/07/11. doi: 10.1146/annurev.cellbio.22.010605.093317 16824014.
27. Lebestky T, Chang T, Hartenstein V, Banerjee U. Specification of Drosophila hematopoietic lineage by conserved transcription factors. Science. 2000;288(5463):146–9. Epub 2001/02/07. doi: 10.1126/science.288.5463.146 10753120.
28. Tepass U, Fessler LI, Aziz A, Hartenstein V. Embryonic origin of hemocytes and their relationship to cell death in Drosophila. Development. 1994;120(7):1829–37. Epub 1994/07/01. 7924990.
29. Jung SH, Evans CJ, Uemura C, Banerjee U. The Drosophila lymph gland as a developmental model of hematopoiesis. Development. 2005;132(11):2521–33. Epub 2005/04/29. doi: 10.1242/dev.01837 15857916.
30. Rugendorff A, Younossi-Hartenstein A, Hartenstein V. Embryonic origin and differentiation of the Drosophila heart. Roux Arch Dev Biol. 1994;203(5):266–80. Epub 1994/03/01. doi: 10.1007/BF00360522 28305624.
31. Holz A, Bossinger B, Strasser T, Janning W, Klapper R. The two origins of hemocytes in Drosophila. Development. 2003;130(20):4955–62. Epub 2003/08/22. doi: 10.1242/dev.00702 12930778.
32. Robertson CW. The metamorphosis of Drosophila melanogaster, including an accurately timed account of the principal morphological changes. J Morphol. 1936;59:351–99.
33. Makhijani K, Alexander B, Tanaka T, Rulifson E, Bruckner K. The peripheral nervous system supports blood cell homing and survival in the Drosophila larva. Development. 2011;138(24):5379–91. Epub 2011/11/11. doi: 10.1242/dev.067322 22071105; PubMed Central PMCID: PMC3222213.
34. Stofanko M, Kwon SY, Badenhorst P. A misexpression screen to identify regulators of Drosophila larval hemocyte development. Genetics. 2008;180(1):253–67. Epub 2008/09/02. doi: 10.1534/genetics.108.089094 18757933; PubMed Central PMCID: PMC2535679.
35. Ghosh S, Singh A, Mandal S, Mandal L. Active hematopoietic hubs in Drosophila adults generate hemocytes and contribute to immune response. Dev Cell. 2015;33(4):478–88. Epub 2015/05/12. doi: 10.1016/j.devcel.2015.03.014 25959225; PubMed Central PMCID: PMC4448147.
36. Basu S, Aryan A, Overcash JM, Samuel GH, Anderson MA, Dahlem TJ, et al. Silencing of end-joining repair for efficient site-specific gene insertion after TALEN/CRISPR mutagenesis in Aedes aegypti. Proc Natl Acad Sci U S A. 2015;112(13):4038–43. Epub 2015/03/17. doi: 10.1073/pnas.1502370112 25775608; PubMed Central PMCID: PMC4386333.
37. Basu S, Aryan A, Haac ME, Myles KM, Adelman ZN. Methods for TALEN Evaluation, Use, and Mutation Detection in the Mosquito Aedes aegypti. Methods Mol Biol. 2016;1338:157–77. Epub 2015/10/08. doi: 10.1007/978-1-4939-2932-0_13 26443221; PubMed Central PMCID: PMC5013829.
38. Nasci RS. Relationship of wing length to adult dry weight in several mosquito species (Diptera: Culicidae). J Med Entomol. 1990;27(4):716–9. Epub 1990/07/01. doi: 10.1093/jmedent/27.4.716 2388250.
39. Ramirez CE, Nouzova M, Benigni P, Quirke JME, Noriega FG, Fernandez-Lima F. Fast, ultra-trace detection of juvenile hormone III from mosquitoes using mass spectrometry. Talanta. 2016;159:371–8. Epub 2016/07/31. doi: 10.1016/j.talanta.2016.06.041 27474320; PubMed Central PMCID: PMC5659872.
40. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7):676–82. Epub 2012/06/30. doi: 10.1038/nmeth.2019 22743772; PubMed Central PMCID: PMC3855844.
41. Castillo JC, Robertson AE, Strand MR. Characterization of hemocytes from the mosquitoes Anopheles gambiae and Aedes aegypti. Insect Biochem Mol Biol. 2006;36(12):891–903. Epub 2006/11/14. doi: 10.1016/j.ibmb.2006.08.010 17098164; PubMed Central PMCID: PMC2757042.
42. Rao X, Huang X, Zhou Z, Lin X. An improvement of the 2^(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis. Biostat Bioinforma Biomath. 2013;3(3):71–85. Epub 2013/08/01. 25558171; PubMed Central PMCID: PMC4280562.
43. Ramirez JL, Garver LS, Brayner FA, Alves LC, Rodrigues J, Molina-Cruz A, et al. The Role of Hemocytes in Anopheles gambiae Antiplasmodial Immunity. J Innate Immun. 2014;6(2):119–28. doi: 10.1159/000353765 WOS:000331774900002. 23886925
Článek vyšel v časopise
PLOS Pathogens
2020 Číslo 1
- Může hubnutí souviset s vyšším rizikem nádorových onemocnění?
- Raději si zajděte na oční! Jak souvisí citlivost zraku s rozvojem demence?
- Co způsobuje pooperační infekce? Na vině může být i naše vlastní mikrobiota
- Čeká nás průlom v diagnostice karcinomu pankreatu?
- Polibek, který mi „vzal nohy“ aneb vzácný výskyt EBV u 70leté ženy – kazuistika
Nejčtenější v tomto čísle
- Chromatin maturation of the HIV-1 provirus in primary resting CD4+ T cells
- Hydropic anthelmintics against parasitic nematodes
- Norovirus infection results in eIF2α independent host translation shut-off and remodels the G3BP1 interactome evading stress granule formation
- Modular Mimicry and Engagement of the Hippo Pathway by Marburg Virus VP40: Implications for Filovirus Biology and Budding