蚊虫对病原体的免疫机制研究

doi:10.11853/j.issn.1003.4692.2013.06.001

摘要/Abstract

摘要：

蚊虫是重要的虫媒疾病传播媒介，可传播多种疾病，如疟疾、登革热等，严重危害人类健康。媒介蚊虫的防治是控制此类传染病的重要措施。蚊虫依赖天然免疫系统抵御疟原虫、真菌、病毒等外源病原体的侵染。蚊虫免疫主要分为体液免疫和细胞免疫。补体识别激活系统、免疫信号通路、黑化反应和活性氧等途径均参与了对病原体的免疫反应。现就媒介蚊虫抵御疟原虫和真菌等病原体免疫应答机制的最新进展进行综述。这将为发展新的蚊虫控制策略提供理论支持。

关键词: 蚊虫, 体液免疫, 细胞免疫, 疟原虫, 虫生真菌

Abstract:

As an important vector for insect-borne diseases, mosquitoes transmit viral encephalitis, dengue, malaria, filariasis and others and cause great concern to human health. The prevention and control of mosquito vectors is an important measure for controlling these infectious diseases. Mosquitoes have developed innate immunity against pathogens such as viruses, fungi and parasites. The immunity of mosquitoes is mainly classified into humoral immunity and cellular immunity. Complement recognition and activation system, immune signaling pathways, melanization, reactive oxygen species, etc. are involved in the immune response to pathogens. This paper reviews the recent research progress in the immune response mechanism against pathogens such as malaria parasites and fungi in mosquito vectors, which will provide theoretical support for developing new mosquito control strategies.

Key words: Mosquito, Humoral immunity, Cellular immunity, Plasmodium, Entomogenous fungus

中图分类号:

R384.1

王燕红, 王举梅, 江红, 邹振. 蚊虫对病原体的免疫机制研究[J]. 中国媒介生物学及控制杂志, 2013, 24(6): 477-482.

WANG Yan-hong, WANG Ju-mei, JIANG Hong, ZOU Zhen. Research advances on immune mechanism against pathogens in mosquitoes[J]. Chines Journal of Vector Biology and Control, 2013, 24(6): 477-482.

参考文献

[1] World Health Organization. World malaria report 2008
[M]. Geneva: W HO/HTM/GMP,2008：1.

[2] Cirimotich CM,Dong Y,Garver LS,et al. Mosquito immune d efenses against Plasmodium infection
[J]. Dev Comp Immunol, 2 010,34(4)：387-395.

[3] Hoffmann JA,Reichhart JM. Drosophila innate immunity：an e volutionary perspective
[J]. Nat Immunol,2002,3(2)：121-126.

[4] Lemaitre B, Hoffmann J. The host defense of Drosophila m elanogaster
[J]. Annu Rev Immunol,2007,25：697-743.

[5] Hultmark D. Drosophila immunity：Paths and patterns
[J]. Curr O pin Immunol,2003,15(1)：12-19.

[6] Meister M. Blood cells of Drosophila：cell lineages and role in host d efence
[J]. Curr Opin Immunol,2004,16(1)：10-15.

[7] Blandin S,Shiao SH,Moita LF,et al. Complement-like protein T EP 1 is a determinant of vectorial capacity in the malaria vector A nopheles gambiae
[J]. Cell,2004,116(5)：661-670.

[8] Alavi Y,Arai M,Mendoza J,et al. The dynamics of interactions b etween Plasmodium and the mosquito：a study of the infectivity of P lasmodium berghei and Plasmodium gallinaceum, and their t ransmission by Anopheles stephensi,Anopheles gambiae and Aedes a egypti
[J]. Int J Parasitol,2003,33(9)：933-943.

[9] Blandin S, Levashina EA. Mosquito immune responses against m alaria parasites
[J]. Curr Opin Immunol,2004,16(1)：16-20.

[10] Hillyer JF,Barreau C,Vernick KD. Efficiency of salivary gland i nvasion by malaria sporozoites is controlled by rapid sporozoite d estruction in the mosquito haemocoel
[J]. Int J Parasitol,2007,37 ( 6)：673-681.

[11] Sinden RE. Plasmodium differentiation in the mosquito
[J]. P arassitologia,1999,41(1/3)：139-148.

[12] Bartholomay LC,Waterhouse RM,Mayhew GF,et al. Pathogenomics o f Culex quinquefasciatus and meta-analysis of infection responses to d iverse pathogens
[J]. Science,2010,330(6000)：88-90.

[13] Christophides GK,Zdobnov E,Barillas-Mury C,et al. Immunity- r elated genes and gene families in Anopheles gambiae
[J]. Science, 2 002,298(5591)：159-165.

[14] Waterhouse RM,Kriventseva EV,Meister S,et al. Evolutionary d ynamics of immune-related genes and pathways in disease-vector m osquitoes
[J]. Science,2007,316(5832)：1738-1743.

[15] Kanost MR,Jiang H,Yu XQ. Innate immune responses of a l epidopteran insect,Manduca sexta
[J]. Immunol Rev,2004,198： 9 7-105.

[16] Collins FH,Sakai RK,Vernick KD,et al. Genetic selection of a P lasmodium - refractory strain of the malaria vector Anopheles g ambiae
[J]. Science,1986,234(4776)：607-610.

[17] de Gregorio E,Spellman PT,Tzou P,et al. The Toll and Imd p athways are the major regulators of the immune response in D rosophila
[J]. EMBO J,2002,21(11)：2568-2579.

[18] Dostert C,Jouanguy E,Irving P,et al. The Jak-STAT signaling p athway is required but not sufficient for the antiviral response of D rosophila
[J]. Nat Immunol,2005,6(9)：946-953.

[19] Xi Z,Ramirez JL,Dimopoulos G. The Aedes aegypti toll pathway c ontrols dengue virus infection
[J]. PLoS Pathog,2008,4(7)： e 1000098.

[20] Gupta L,Molina-Cruz A,Kumar S,et al. The STAT pathway m ediates late-phase immunity against Plasmodium in the mosquito A nopheles gambiae
[J]. Cell Host Microbe,2009,5(5)：498-507.

[21] Zou Z,Souza-Neto J,Xi Z,et al. Transcriptome analysis of Aedes a egypti transgenic mosquitoes with altered immunity
[J]. PLoS P athog,2011,7(11)：e1002394.

[22] Dimopoulos G, Christophides GK, Meister S, et al. Genome e xpression analysis of Anopheles gambiae：responses to injury, b acterial challenge,and malaria infection
[J]. Proc Natl Acad Sci U SA,2002,99(13)：8814-8819.

[23] Kokoza V,Ahmed A,Woon Shin S,et al. Blocking of Plasmodium t ransmission by cooperative action of Cecropin A and Defensin A in t ransgenic Aedes aegypti mosquitoes
[J]. Proc Natl Acad Sci USA, 2 010,107(18)：8111-8116.

[24] Cerenius L,Lee BL,Soderhall K. The proPO-system：pros and c ons for its role in invertebrate immunity
[J]. Trends Immunol, 2 008,29(6)：263-271.

[25] Zou Z,Jiang H. Manduca sexta serpin-6 regulates immune serine p roteinases PAP-3 and HP8. cDNA cloning,protein expression, i nhibition kinetics,and function elucidation
[J]. J Biol Chem, 2 005,280(14)：14341-14348.

[26] An C,Budd A,Kanost MR,et al. Characterization of a regulatory u nit that controls melanization and affects longevity of mosquitoes
[J]. Cell Mol Life Sci,2011,68(11)：1929-1939.

[27] Michel K,Budd A,Pinto S,et al. Anopheles gambiae SRPN2 f acilitates midgut invasion by the malaria parasite Plasmodium b erghei
[J]. EMBO Rep,2005,6(9)：891-897.

[28] Michel K, Suwanchaichinda C, Morlais I, et al. Increased m elanizing activity in Anopheles gambiae does not affect d evelopment of Plasmodium falciparum
[J]. Proc Natl Acad Sci U SA,2006,103(45)：16858-16863.

[29] Zou Z,Shin SW,Alvarez KS,et al. Distinct melanization pathways i n the mosquito Aedes aegypti
[J]. Immunity,2010,32(1)：41-53.

[30] Molina-Cruz A,DeJong RJ,Charles B,et al. Reactive oxygen s pecies modulate Anopheles gambiae immunity against bacteria and P lasmodium
[J]. J Biol Chem,2008,283(6)：3217-3223.

[31] Ramirez JL,Garver LS,Dimopoulos G. Challenges and approaches f or mosquito targeted malaria control
[J]. Curr Mol Med,2009,9 ( 2)：116-130.

[32] Blandin SA,Marois E,Levashina EA. Antimalarial responses in A nopheles gambiae： from a complement - like protein to a c omplement - like pathway
[J]. Cell Host Microbe,2008,3(6)： 3 64-374.

[33] Osta MA,Christophides GK,Kafatos FC. Effects of mosquito genes o n Plasmodium development
[J]. Science,2004,303(5666)： 2 030-2032.

[34] Osta MA,Christophides GK,Vlachou D,et al. Innate immunity in t he malaria vector Anopheles gambiae：comparative and functional g enomics
[J]. J Exp Biol,2004,207(Pt 15)：2551-2563.

[35] Riehle MM,Markianos K,Niare O,et al. Natural malaria infection i n Anopheles gambiae is regulated by a single genomic control region
[J]. Science,2006,312(5773)：577-579.

[36] Fraiture M, Baxter RH,Steinert S,et al. Two mosquito LRR p roteins function as complement control factors in the T EP1-mediated killing of Plasmodium
[J]. Cell Host Microbe, 2 009,5(3)：273-284.

[37] Frolet C, Thoma M, Blandin S, et al. Boosting NF-kappaB- d ependent basal immunity of Anopheles gambiae aborts development o f Plasmodium berghei
[J]. Immunity,2006,25(4)：677-685.

[38] Garver LS,Dong Y,Dimopoulos G. Caspar controls resistance to P lasmodium falciparum in diverse anopheline species
[J]. PLoS P athog,2009,5(3)：e1000335.

[39] Zheng L,Cornel AJ,Wang R,et al. Quantitative trait loci for r efractoriness of Anopheles gambiae to Plasmodium cynomolgi B
[J]. Science,1997,276(5311)：425-428.

[40] Zou Z,Shin SW,Alvarez KS,et al. Mosquito RUNX4 in the i mmune regulation of PPO gene expression and its effect on avian m alaria parasite infection
[J]. Proc Natl Acad Sci USA,2008,105 ( 47)：18454-18459.

[41] Abraham EG,Pinto SB,Ghosh A,et al. An immune-responsive s erpin, SRPN6, mediates mosquito defense against malaria p arasites
[J]. Proc Natl Acad Sci USA,2005,102(45) ： 1 6327-16332.

[42] Kumar S,Christophides GK,Cantera R,et al. The role of reactive o xygen species on Plasmodium melanotic encapsulation in A nopheles gambiae
[J]. Proc Natl Acad Sci USA,2003,100(24)： 1 4139-14144.

[43] Sinnis P, Jaramillo-Gutierrez G, Molina-Cruz A, et al. The A nopheles gambiae oxidation resistance 1(OXR1)gene regulates e xpression of enzymes that detoxify reactive oxygen species
[J]. P LoS One,2010,5(6)：e11168.

[44] Kumar S, Molina-Cruz A,Gupta L,et al. A peroxidase/dual o xidase system modulates midgut epithelial immunity in Anopheles g ambiae
[J]. Science,2010,327(5973)：1644-1648.

[45] Oliveira Gde A,Lieberman J,Barillas-Mury C. Epithelial nitration b y a peroxidase/NOX5 system mediates mosquito antiplasmodial i mmunity
[J]. Science,2012,335(6070)：856-859.

[46] Cirimotich CM,Dong Y,Clayton AM,et al. Natural microbe- m ediated refractoriness to Plasmodium infection in Anopheles g ambiae
[J]. Science,2011,332(6031)：855-858.

[47] Bian G,Joshi D,Dong Y,et al. Wolbachia invades Anopheles s tephensi populations and induces refractoriness to Plasmodium i nfection
[J]. Science,2013,340(6133)：748-751.

[48] Enayati A,Hemingway J. Malaria management：past,present,and f uture
[J]. Annu Rev Entomol,2010,55：569-591.

[49] Blanford S,Chan BH,Jenkins N,et al. Fungal pathogen reduces p otential for malaria transmission
[J]. Science ,2005,308(5728)： 1 638-1641.

[50] Scholte EJ, Knols BG, Takken W. Infection of the malaria m osquito Anopheles gambiae with the entomopathogenic fungus M etarhizium anisopliae reduces blood feeding and fecundity
[J]. J I nvertebr Pathol,2006,91(1)：43-49.

[51] Kanzok SM,Jacobs-Lorena M. Entomopathogenic fungi as biological i nsecticides to control malaria
[J]. Trends Parasitol,2006,22(2)： 4 9-51.

[52] Scholte EJ,Knols BG,Takken W. Autodissemination of the e ntomopathogenic fungus Metarhizium anisopliae amongst adults of t he malaria vector Anopheles gambiae s.s
[J]. Malar J,2004,3：45.

[53] Clarkson JM,Charnley AK. New insights into the mechanisms of f ungal pathogenesis in insects
[J]. Trends Microbiol,1996,4(5)： 1 97-203.

[54] Ferrandon D,Imler JL,Hetru C,et al. The Drosophila systemic i mmune response： sensing and signalling during bacterial and f ungal infections
[J]. Nat Rev Immunol,2007,7(11)：862-874.

[55] Gottar M,Gobert V,Matskevich AA,et al. Dual detection of f ungal infections in Drosophila via recognition of glucans and s ensing of virulence factors
[J]. Cell,2006,127(7)：1425-1437.

[56] Shin SW, Kokoza V, Bian G, et al. REL1,a homologue of D rosophila dorsal,regulates toll antifungal immune pathway in the f emale mosquito Aedes aegypti
[J]. J Biol Chem,2005,280(16)： 1 6499-16507.

[57] Yassine H,Kamareddine L,Osta MA. The mosquito melanization r esponse is implicated in defense against the entomopathogenic f ungus Beauveria bassiana
[J]. PLoS Pathog,2012,8(11)： e 1003029.

[58] Neafsey DE,Christophides GK,Collins FH,et al. The evolution of t he anopheles 16 genomes project
[J]. G3(Bethesda),2013,3(7)： 1 191-1194. 1 191-1194.