Abstract
Mosquitoes are the vectors of pathogens causing numerous human diseases, including dengue and malaria. Due to increases in drug resistance among pathogens or the lack of effective treatments for these diseases and increasing insecticide resistance among mosquito populations, new methods of control are urgently needed to limit the morbidity and mortality caused by vector-borne diseases. Mosquitoes possess an innate immune system capable of limiting infection with human pathogens, and the creation and deployment of transgenic mosquitoes with an enhanced immune system has been suggested as a novel means to reduce mosquito vector competence. However, activation of the immune system is often associated with a cost to the host, which could limit the ability of the transgenic insects to replace their wild-type conspecifics. Here, we discuss recent research into the effects of increased immune deployment and insect transgenesis on the fitness of the mosquitoes.
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References
Aguilar R, Jedlicka AE, Mintz M, Mahairaki V, Scott AL and Dimopoulos G (2005) Global gene expression analysis of Anopheles gambiae responses to microbial challenge. Insect Biochem Mol Biol 35: 709-719.
Amenya DA, Bonizzoni M, Isaacs AT, Jasinskiene N, Chen H, Marinotti O, Yan G and James AA (2010) Comparative fitness assessment of Anopheles stephensi transgenic lines receptive to site-specific integration. Insect Mol Biol 19: 263-269.
Anderson RA, Knols BG and Koella JC (2000) Plasmodium falciparum sporozoites increase feeding-associated mortality of their mosquito hosts Anopheles gambiae s.l. Parasitology 120: 329-333.
Antonova Y, Alvarez KS, Kim YJ, Kokoza V and Raikhel AS (2009) The role of NF-kappaB factor REL2 in the Aedes aegypti immune response. Insect Biochem Mol Biol 39: 303-314.
Barillas-Mury C, Charlesworth A, Gross I, Richman A, Hoffmann JA and Kafatos FC (1996) Immune factor Gambif1, a new rel family member from the human malaria vector, Anopheles gambiae. EMBO J 15: 4691-4701.
Bedhomme S, Agnew P, Sidobre C and Michalakis Y (2004) Virulence reaction norms across a food gradient. Proc Biol Sci 271: 739-744.
Bian G, Shin SW, Cheon HM, Kokoza V and Raikhel AS (2005) Transgenic alteration of Toll immune pathway in the female mosquito Aedes aegypti. Proc Natl Acad Sci USA 102: 13568-13573.
Blandin S, Shiao SH, Moita LF, Janse CJ, Waters AP, Kafatos FC and Levashina EA (2004) Complement-like protein TEP1 is a determinant of vectorial capacity in the malaria vector Anopheles gambiae. Cell 116: 661-670.
Catteruccia F, Nolan T, Loukeris TG, Blass C, Savakis C, Kafatos FC and Crisanti A (2000) Stable germline transformation of the malaria mosquito Anopheles stephensi. Nature 405: 959-962.
Christophides GK, Zdobnov E, Barillas-Mury C, Birney E, Blandin S, Blass C, Brey PT, Collins FH, Danielli A, Dimopoulos G, Hetru C, Hoa NT, Hoffmann JA, Kanzok SM, Letunic I, Levashina EA, Loukeris TG, Lycett G, Meister S, Michel K, Moita LF, Muller HM, Osta MA, Paskewitz SM, Reichhart JM, Rzhetsky A, Troxler L, Vernick KD, Vlachou D, Volz J, von Mering C, Xu J, Zheng L, Bork P and Kafatos FC (2002) Immunity-related genes and gene families in Anopheles gambiae. Science 298: 159-165.
Cirimotich CM, Clayton AM and Dimopoulos G (2011) Low- and high-tech approaches to control Plasmodium parasite transmission by Anopheles mosquitoes. J Trop Med 2011: 891342.
Cirimotich CM, Dong Y, Garver LS, Sim S and Dimopoulos G (2010) Mosquito immune defenses against Plasmodium infection. Dev Comp Immunol 34: 387-395.
Coates CJ, Jasinskiene N, Miyashiro L and James AA (1998) Mariner transposition and transformation of the yellow fever mosquito, Aedes aegypti. Proc Natl Acad Sci USA 95: 3748-3751.
De Gregorio E, Spellman PT, Rubin GM and Lemaitre B (2001) Genome-wide analysis of the Drosophila immune response by using oligonucleotide microarrays. Proc Natl Acad Sci USA 98: 12590-12595.
DeVeale B, Brummel T and Seroude L (2004) Immunity and aging: the enemy within? Aging Cell 3: 195-208.
DiAngelo JR, Bland ML, Bambina S, Cherry S and Birnbaum MJ (2009) The immune response attenuates growth and nutrient storage in Drosophila by reducing insulin signaling. Proc Natl Acad Sci USA 106: 20853-20858.
Dong Y, Aguilar R, Xi Z, Warr E, Mongin E and Dimopoulos G (2006) Anopheles gambiae immune responses to human and rodent Plasmodium parasite species. PLoS Pathog 2: e52.
Dong Y, Das S, Cirimotich C, Souza-Neto JA, McLean KJ and Dimopoulos G (2011) Engineered anopheles immunity to Plasmodium infection. PLoS Pathog 7: e1002458.
Dong Y, Manfredini F and Dimopoulos G (2009) Implication of the mosquito midgut microbiota in the defense against malaria parasites. PLoS Pathog 5: e1000423.
Franz AW, Sanchez-Vargas I, Adelman ZN, Blair CD, Beaty BJ, James AA and Olson KE (2006) Engineering RNA interference-based resistance to dengue virus type 2 in genetically modified Aedes aegypti. Proc Natl Acad Sci USA 103: 4198-4203.
Frolet C, Thoma M, Blandin S, Hoffmann JA and Levashina EA (2006) Boosting NF-kappaB-dependent basal immunity of Anopheles gambiae aborts development of Plasmodium berghei. Immunity 25: 677-685.
Garver LS, Dong Y and Dimopoulos G (2009) Caspar controls resistance to Plasmodium falciparum in diverse anopheline species. PLoS Pathog 5: e1000335.
Grossman GL, Rafferty CS, Clayton JR, Stevens TK, Mukabayire O and Benedict MQ (2001) Germline transformation of the malaria vector, Anopheles gambiae, with the piggyBac transposable element. Insect Mol Biol 10: 597-604.
Gupta L, Molina-Cruz A, Kumar S, Rodrigues J, Dixit R, Zamora RE and Barillas-Mury C (2009) The STAT pathway mediates late-phase immunity against Plasmodium in the mosquito Anopheles gambiae. Cell Host Microbe 5: 498-507.
Hogg JC and Hurd H (1995) Plasmodium yoelii nigeriensis: the effect of high and low intensity of infection upon the egg production and bloodmeal size of Anopheles stephensi during three gonotrophic cycles. Parasitology 111 (Pt 5): 555-562.
Holt RA, Subramanian GM, Halpern A, Sutton GG, Charlab R, Nusskern DR, Wincker P, Clark AG, Ribeiro JM, Wides R, Salzberg SL, Loftus B, Yandell M, Majoros WH, Rusch DB, Lai Z, Kraft CL, Abril JF, Anthouard V, Arensburger P, Atkinson PW, Baden H, de Berardinis V, Baldwin D, Benes V, Biedler J, Blass C, Bolanos R, Boscus D, Barnstead M, Cai S, Center A, Chaturverdi K, Christophides GK, Chrystal MA, Clamp M, Cravchik A, Curwen V, Dana A, Delcher A, Dew I, Evans CA, Flanigan M, Grundschober-Freimoser A, Friedli L, Gu Z, Guan P, Guigo R, Hillenmeyer ME, Hladun SL, Hogan JR, Hong YS, Hoover J, Jaillon O, Ke Z, Kodira C, Kokoza E, Koutsos A, Letunic I, Levitsky A, Liang Y, Lin JJ, Lobo NF, Lopez JR, Malek JA, McIntosh TC, Meister S, Miller J, Mobarry C, Mongin E, Murphy SD, O’Brochta DA, Pfannkoch C, Qi R, Regier MA, Remington K, Shao H, Sharakhova MV, Sitter CD, Shetty J, Smith TJ, Strong R, Sun J, Thomasova D, Ton LQ, Topalis P, Tu Z, Unger MF, Walenz B, Wang A, Wang J, Wang M, Wang X, Woodford KJ, Wortman JR, Wu M, Yao A, Zdobnov EM, Zhang H, Zhao Q, Zhao S, Zhu SC, Zhimulev I, Coluzzi M, della Torre A, Roth CW, Louis C, Kalush F, Mural RJ, Myers EW, Adams MD, Smith HO, Broder S, Gardner MJ, Fraser CM, Birney E, Bork P, Brey PT, Venter JC, Weissenbach J, Kafatos FC, Collins FH and Hoffman SL (2002) The genome sequence of the malaria mosquito Anopheles gambiae. Science 298: 129-149.
Hurd H, Taylor PJ, Adams D, Underhill A and Eggleston P (2005) Evaluating the costs of mosquito resistance to malaria parasites. Evolution 59: 2560-2572.
Imroze K and Prasad NG (2011) Sex-specific effect of bacterial infection on components of adult fitness in Drosophila melanogaster. J Evol Biol Res 3: 79-86.
Isaacs AT, Li F, Jasinskiene N, Chen X, Nirmala X, Marinotti O, Vinetz JM and James AA (2011) Engineered resistance to Plasmodium falciparum development in transgenic Anopheles stephensi. PLoS Pathog 7: e1002017.
Jasinskiene N, Coates CJ, Benedict MQ, Cornel AJ, Rafferty CS, James AA and Collins FH (1998) Stable transformation of the yellow fever mosquito, Aedes aegypti, with the Hermes element from the housefly. Proc Natl Acad Sci USA 95: 3743-3747.
Khoo CC, Piper J, Sanchez-Vargas I, Olson KE and Franz AW (2010) The RNA interference pathway affects midgut infection- and escape barriers for Sindbis virus in Aedes aegypti. BMC Microbiol 10: 130.
Koenraadt CJ, Kormaksson M and Harrington LC (2010) Effects of inbreeding and genetic modification on Aedes aegypti larval competition and adult energy reserves. Parasit Vectors 3: 92.
Kokoza V, Ahmed A, Woon Shin S, Okafor N, Zou Z and Raikhel AS (2010) Blocking of Plasmodium transmission by cooperative action of Cecropin A and Defensin A in transgenic Aedes aegypti mosquitoes. Proc Natl Acad Sci USA 107: 8111-8116.
Kraaijeveld AR, Ferrari J and Godfray HC (2002) Costs of resistance in insect-parasite and insect-parasitoid interactions. Parasitology 125 Suppl: S71-82.
Labbe GM, Nimmo DD and Alphey L (2010) piggybac- and PhiC31-mediated genetic transformation of the Asian tiger mosquito, Aedes albopictus (Skuse). PLoS Negl Trop Dis 4: e788.
Levashina EA, Moita LF, Blandin S, Vriend G, Lagueux M and Kafatos FC (2001) Conserved role of a complement-like protein in phagocytosis revealed by dsRNA knockout in cultured cells of the mosquito, Anopheles gambiae. Cell 104: 709-718.
Li C, Marrelli MT, Yan G and Jacobs-Lorena M (2008) Fitness of transgenic Anopheles stephensi mosquitoes expressing the SM1 peptide under the control of a vitellogenin promoter. J Hered 99: 275-282.
Libert S, Chao Y, Chu X and Pletcher SD (2006) Trade-offs between longevity and pathogen resistance in Drosophila melanogaster are mediated by NFkappaB signaling. Aging Cell 5: 533-543.
Luna C, Hoa NT, Lin H, Zhang L, Nguyen HL, Kanzok SM and Zheng L (2006) Expression of immune responsive genes in cell lines from two different Anopheline species. Insect Mol Biol 15: 721-729.
MacDonald G (1957) The epidemiology and control of malaria. Oxford University Press, London, UK.
Marrelli MT, Li C, Rasgon JL and Jacobs-Lorena M (2007) Transgenic malaria-resistant mosquitoes have a fitness advantage when feeding on Plasmodium-infected blood. Proc Natl Acad Sci USA 104: 5580-5583.
Marrelli MT, Moreira CK, Kelly D, Alphey L and Jacobs-Lorena M (2006) Mosquito transgenesis: what is the fitness cost? Trends Parasitol 22: 197-202.
Mathur G, Sanchez-Vargas I, Alvarez D, Olson KE, Marinotti O and James AA (2010) Transgene-mediated suppression of dengue viruses in the salivary glands of the yellow fever mosquito, Aedes aegypti. Insect Mol Biol 19: 753-763.
McKean KA and Nunney L (2001) Increased sexual activity reduces male immune function in Drosophila melanogaster. Proc Natl Acad Sci USA 98: 7904-7909.
McKean KA, Yourth CP, Lazzaro BP and Clark AG (2008) The evolutionary costs of immunological maintenance and deployment. BMC Evol Biol 8: 76.
Meister S, Agianian B, Turlure F, Relogio A, Morlais I, Kafatos FC and Christophides GK (2009) Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites. PLoS Pathog 5: e1000542.
Meister S, Kanzok SM, Zheng XL, Luna C, Li TR, Hoa NT, Clayton JR, White KP, Kafatos FC, Christophides GK and Zheng L (2005) Immune signaling pathways regulating bacterial and malaria parasite infection of the mosquito Anopheles gambiae. Proc Natl Acad Sci USA 102: 11420-11425.
Meredith JM, Basu S, Nimmo DD, Larget-Thiery I, Warr EL, Underhill A, McArthur CC, Carter V, Hurd H, Bourgouin C and Eggleston P (2011) Site-specific integration and expression of an anti-malarial gene in transgenic Anopheles gambiae significantly reduces Plasmodium infections. PLoS ONE 6: e14587.
Mitri C, Jacques JC, Thiery I, Riehle MM, Xu J, Bischoff E, Morlais I, Nsango SE, Vernick KD and Bourgouin C (2009) Fine pathogen discrimination within the APL1 gene family protects Anopheles gambiae against human and rodent malaria species. PLoS Pathog 5: e1000576.
Moita LF, Wang-Sattler R, Michel K, Zimmermann T, Blandin S, Levashina EA and Kafatos FC (2005) in vivo identification of novel regulators and conserved pathways of phagocytosis in A. gambiae. Immunity 23: 65-73.
Nene V, Wortman JR, Lawson D, Haas B, Kodira C, Tu ZJ, Loftus B, Xi Z, Megy K, Grabherr M, Ren Q, Zdobnov EM, Lobo NF, Campbell KS, Brown SE, Bonaldo MF, Zhu J, Sinkins SP, Hogenkamp DG, Amedeo P, Arensburger P, Atkinson PW, Bidwell S, Biedler J, Birney E, Bruggner RV, Costas J, Coy MR, Crabtree J, Crawford M, Debruyn B, Decaprio D, Eiglmeier K, Eisenstadt E, El-Dorry H, Gelbart WM, Gomes SL, Hammond M, Hannick LI, Hogan JR, Holmes MH, Jaffe D, Johnston JS, Kennedy RC, Koo H, Kravitz S, Kriventseva EV, Kulp D, Labutti K, Lee E, Li S, Lovin DD, Mao C, Mauceli E, Menck CF, Miller JR, Montgomery P, Mori A, Nascimento AL, Naveira HF, Nusbaum C, O’Leary S, Orvis J, Pertea M, Quesneville H, Reidenbach KR, Rogers YH, Roth CW, Schneider JR, Schatz M, Shumway M, Stanke M, Stinson EO, Tubio JM, Vanzee JP, Verjovski-Almeida S, Werner D, White O, Wyder S, Zeng Q, Zhao Q, Zhao Y, Hill CA, Raikhel AS, Soares MB, Knudson DL, Lee NH, Galagan J, Salzberg SL, Paulsen IT, Dimopoulos G, Collins FH, Birren B, Fraser-Liggett CM and Severson DW (2007) Genome sequence of Aedes aegypti, a major arbovirus vector. Science 316: 1718-1723.
Nimmo DD, Alphey L, Meredith JM and Eggleston P (2006) High efficiency site-specific genetic engineering of the mosquito genome. Insect Mol Biol 15: 129-136.
Perera OP, Harrell IR and Handler AM (2002) Germ-line transformation of the South American malaria vector, Anopheles albimanus, with a piggyBac/EGFP transposon vector is routine and highly efficient. Insect Mol Biol 11: 291-297.
Ramirez JL and Dimopoulos G (2010) The Toll immune signaling pathway control conserved anti-dengue defenses across diverse Ae. aegypti strains and against multiple dengue virus serotypes. Dev Comp Immunol 34: 625-629.
Sharmila Bharathi N, Archana N, Badrinarayanan A, Satish KM, Mohan J and Joshi A (2007) Time to death in the presence of E. coli: a mass-scale method for assaying pathogen resistance in Drosophila. J Genet 86: 75-79.
Shin SW, Kokoza V, Ahmed A and Raikhel AS (2002) Characterization of three alternatively spliced isoforms of the Rel/NF-kappa B transcription factor Relish from the mosquito Aedes aegypti. Proc Natl Acad Sci U S A 99: 9978-9983.
Shin SW, Kokoza V, Bian G, Cheon HM, Kim YJ and Raikhel AS (2005) REL1, a homologue of Drosophila dorsal, regulates toll antifungal immune pathway in the female mosquito Aedes aegypti. J Biol Chem 280: 16499-16507.
Shin SW, Kokoza V, Lobkov I and Raikhel AS (2003) Relish-mediated immune deficiency in the transgenic mosquito Aedes aegypti. Proc Natl Acad Sci USA 100: 2616-2621.
Smith DL and McKenzie FE (2004) Statics and dynamics of malaria infection in Anopheles mosquitoes. Malar J 3: 13.
Souza-Neto JA, Sim S and Dimopoulos G (2009) An evolutionary conserved function of the JAK-STAT pathway in anti-dengue defense. Proc Natl Acad Sci USA 106: 17841-17846.
Voordouw MJ, Koella JC and Hurd H (2008) Comparison of male reproductive success in malaria-refractory and susceptible strains of Anopheles gambiae. Malar J 7: 103.
Walker T and Moreira LA (2011) Can Wolbachia be used to control malaria? Mem Inst Oswaldo Cruz 106 Suppl 1: 212-217.
Wilson C, Bellen HJ and Gehring WJ (1990) Position effects on eukaryotic gene expression. Annu Rev Cell Biol 6: 679-714.
Windbichler N, Papathanos PA, Catteruccia F, Ranson H, Burt A and Crisanti A (2007) Homing endonuclease mediated gene targeting in Anopheles gambiae cells and embryos. Nucleic Acids Res 35: 5922-5933.
Yan G, Severson DW and Christensen BM (1997) Costs and benefits of mosquito refractoriness to malaria parasites: implications for genetic variability of mosquitoes and genetic control of malaria. Evolution 51: 441-450.
Xi Z, Ramirez JL and Dimopoulos G (2008) The Aedes aegypti toll pathway controls dengue virus infection. PLoS Pathog 4: e1000098.
Zerofsky M, Harel E, Silverman N and Tatar M (2005) Aging of the innate immune response in Drosophila melanogaster. Aging Cell 4: 103-108.
Zhou G, Kohlhepp P, Geiser D, Frasquillo Mdel C, Vazquez-Moreno L and Winzerling JJ (2007) Fate of blood meal iron in mosquitoes. J Insect Physiol 53: 1169-1178.
Zou Z, Shin SW, Alvarez KS, Bian G, Kokoza V and Raikhel AS (2008) Mosquito RUNX4 in the immune regulation of PPO gene expression and its effect on avian malaria parasite infection. Proc Natl Acad Sci USA 105: 18454-18459.
Zou Z, Souza-Neto J, Xi Z, Kokoza V, Shin SW, Dimopoulos G and Raikhel A (2011) Transcriptome analysis of Aedes aegypti transgenic mosquitoes with altered immunity. PLoS Pathog 7: e1002394.
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Pike, A.D., Cirimotich, C.M., Dimopoulos, G. (2013). Impact of transgenic immune deployment on mosquito fitness. In: Ecology of parasite-vector interactions. Ecology and control of vector-borne diseases, vol 3. Wageningen Academic Publishers, Wageningen. https://doi.org/10.3920/978-90-8686-744-8_2
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