The STAT Pathway Mediates Late-phase Immunity Against Plasmodium in the Mosquito Anopheles Gambiae

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2009 May 21

PMID 19454353

Citations 106

Authors

Lalita Gupta

Alvaro Molina-Cruz

Sanjeev Kumar

Janneth Rodrigues

Rajnikant Dixit

Rodolfo E Zamora

Carolina Barillas-Mury

Affiliations

Soon will be listed here.

Abstract

The STAT family of transcription factors activates expression of immune system genes in vertebrates. The ancestral STAT gene (AgSTAT-A) appears to have duplicated in the mosquito Anopheles gambiae, giving rise to a second intronless STAT gene (AgSTAT-B), which we show regulates AgSTAT-A expression in adult females. AgSTAT-A participates in the transcriptional activation of nitric oxide synthase (NOS) in response to bacterial and plasmodial infection. Activation of this pathway, however, is not essential for mosquitoes to survive a bacterial challenge. AgSTAT-A silencing reduces the number of early Plasmodium oocysts in the midgut, but nevertheless enhances the overall infection by increasing oocyst survival. Silencing of SOCS, a STAT suppressor, has the opposite effect, reducing Plasmodium infection by increasing NOS expression. Chemical inhibition of mosquito NOS activity after oocyte formation increases oocyte survival. Thus, the AgSTAT-A pathway mediates a late-phase antiplasmodial response that reduces oocyst survival in A. gambiae.

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References

Harrison D, Binari R, Nahreini T, Gilman M, Perrimon N . Activation of a Drosophila Janus kinase (JAK) causes hematopoietic neoplasia and developmental defects. EMBO J. 1995; 14(12):2857-65. PMC: 398404. DOI: 10.1002/j.1460-2075.1995.tb07285.x. View

Billker O, Shaw M, Margos G, Sinden R . The roles of temperature, pH and mosquito factors as triggers of male and female gametogenesis of Plasmodium berghei in vitro. Parasitology. 1997; 115 ( Pt 1):1-7. DOI: 10.1017/s0031182097008895. View

Betz A, Lampen N, Martinek S, YOUNG M, Darnell Jr J . A Drosophila PIAS homologue negatively regulates stat92E. Proc Natl Acad Sci U S A. 2001; 98(17):9563-8. PMC: 55492. DOI: 10.1073/pnas.171302098. View

Castillo J, Robertson A, Strand M . Characterization of hemocytes from the mosquitoes Anopheles gambiae and Aedes aegypti. Insect Biochem Mol Biol. 2006; 36(12):891-903. PMC: 2757042. DOI: 10.1016/j.ibmb.2006.08.010. View

Dostert C, Jouanguy E, Irving P, Troxler L, Galiana-Arnoux D, Hetru C . The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila. Nat Immunol. 2005; 6(9):946-53. DOI: 10.1038/ni1237. View

Luckhart S, Vodovotz Y, Cui L, Rosenberg R . The mosquito Anopheles stephensi limits malaria parasite development with inducible synthesis of nitric oxide. Proc Natl Acad Sci U S A. 1998; 95(10):5700-5. PMC: 20442. DOI: 10.1073/pnas.95.10.5700. View

Schindler C, Levy D, Decker T . JAK-STAT signaling: from interferons to cytokines. J Biol Chem. 2007; 282(28):20059-63. DOI: 10.1074/jbc.R700016200. View

Garver L, Xi Z, Dimopoulos G . Immunoglobulin superfamily members play an important role in the mosquito immune system. Dev Comp Immunol. 2007; 32(5):519-31. PMC: 2483948. DOI: 10.1016/j.dci.2007.09.007. View

Kim L, Choi U, Cho H, Lee J, Lee W, Kim J . Down-regulation of NF-kappaB target genes by the AP-1 and STAT complex during the innate immune response in Drosophila. PLoS Biol. 2007; 5(9):e238. PMC: 1964775. DOI: 10.1371/journal.pbio.0050238. View

10.

Abraham E, Pinto S, Ghosh A, Vanlandingham D, Budd A, Higgs S . An immune-responsive serpin, SRPN6, mediates mosquito defense against malaria parasites. Proc Natl Acad Sci U S A. 2005; 102(45):16327-32. PMC: 1283470. DOI: 10.1073/pnas.0508335102. View

11.

Franke-Fayard B, Trueman H, Ramesar J, Mendoza J, van der Keur M, van der Linden R . A Plasmodium berghei reference line that constitutively expresses GFP at a high level throughout the complete life cycle. Mol Biochem Parasitol. 2004; 137(1):23-33. DOI: 10.1016/j.molbiopara.2004.04.007. View

12.

Tanji T, Ip Y . Regulators of the Toll and Imd pathways in the Drosophila innate immune response. Trends Immunol. 2005; 26(4):193-8. DOI: 10.1016/j.it.2005.02.006. View

13.

Foley E, OFarrell P . Nitric oxide contributes to induction of innate immune responses to gram-negative bacteria in Drosophila. Genes Dev. 2003; 17(1):115-25. PMC: 195964. DOI: 10.1101/gad.1018503. View

14.

Hoffmann J, Reichhart J . Drosophila innate immunity: an evolutionary perspective. Nat Immunol. 2002; 3(2):121-6. DOI: 10.1038/ni0202-121. View

15.

Muller H, Dimopoulos G, Blass C, Kafatos F . A hemocyte-like cell line established from the malaria vector Anopheles gambiae expresses six prophenoloxidase genes. J Biol Chem. 1999; 274(17):11727-35. DOI: 10.1074/jbc.274.17.11727. View

16.

Christophides G, Zdobnov E, Barillas-Mury C, Birney E, Blandin S, Blass C . Immunity-related genes and gene families in Anopheles gambiae. Science. 2002; 298(5591):159-65. DOI: 10.1126/science.1077136. View

17.

TRAGER W, Jensen J . Human malaria parasites in continuous culture. Science. 1976; 193(4254):673-5. DOI: 10.1126/science.781840. View

18.

Alavi Y, Arai M, Mendoza J, Tufet-Bayona M, Sinha R, Fowler K . The dynamics of interactions between Plasmodium and the mosquito: a study of the infectivity of Plasmodium berghei and Plasmodium gallinaceum, and their transmission by Anopheles stephensi, Anopheles gambiae and Aedes aegypti. Int J Parasitol. 2003; 33(9):933-43. DOI: 10.1016/s0020-7519(03)00112-7. View

19.

Wormald S, Hilton D . Inhibitors of cytokine signal transduction. J Biol Chem. 2003; 279(2):821-4. DOI: 10.1074/jbc.R300030200. View

20.

Krzemien J, Dubois L, Makki R, Meister M, Vincent A, Crozatier M . Control of blood cell homeostasis in Drosophila larvae by the posterior signalling centre. Nature. 2007; 446(7133):325-8. DOI: 10.1038/nature05650. View