Regulation of Anti- Immunity by a -like Transcription Factor in the Malaria Vector

English version České info

The mosquito is the obligate vector for malaria transmission. To complete its development within the mosquito, the malaria parasite Plasmodium must overcome the protective action of the mosquito innate immune system. Here we report on the involvement of the Anopheles gambiae orthologue of a conserved component of the vertebrate immune system, LPS-induced TNFα transcription factor (LITAF), and its role in mosquito anti-Plasmodium immunity. An. gambiae LITAF-like 3 (LL3) expression is up-regulated in response to midgut invasion by both rodent and human malaria parasites. Silencing of LL3 expression greatly increases parasite survival, indicating that LL3 is part of an anti-Plasmodium defense mechanism. Electrophoretic mobility shift assays identified specific LL3 DNA-binding motifs within the promoter of SRPN6, a gene that also mediates mosquito defense against Plasmodium. Further experiments indicated that these motifs play a direct role in LL3 regulation of SRPN6 expression. We conclude that LL3 is a transcription factor capable of modulating SRPN6 expression as part of the mosquito anti-Plasmodium immune response.

Vyšlo v časopise: Regulation of Anti- Immunity by a -like Transcription Factor in the Malaria Vector. PLoS Pathog 8(10): e32767. doi:10.1371/journal.ppat.1002965
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002965

Souhrn

Zdroje

1. MacEwanDJ (2002) TNF receptor subtype signalling: differences and cellular consequences. Cell Signal 14: 477–492.

2. MyokaiF, TakashibaS, LeboR, AmarS (1999) A novel lipopolysaccharide-induced transcription factor regulating tumor necrosis factor alpha gene expression: molecular cloning, sequencing, characterization, and chromosomal assignment. Proc Natl Acad Sci USA 96: 4518–4523.

3. TangX, FentonM, AmarS (2003) Identification and functional characterization of a novel binding site on TNF-α promoter. Proc Natl Acad Sci USA 100: 4096–4101.

4. TangX, MetzgerD, LeemanS, AmarS (2006) LPS-induced TNFa factor (LITAF)-deficient mice express reduced LPS-induced cytokine: Evidence for LITAF-dependent LPS signaling pathways. Proc Natl Acad Sci USA 103: 1–6.

5. FroletC, ThomaM, BlandinS, HoffmannJA, LevashinaEA (2006) Boosting NF-kappaB-dependent basal immunity of Anopheles gambiae aborts development of Plasmodium berghei. Immunity 25: 677–685.

6. GarverLS, DongY, DimopoulosG (2009) Caspar controls resistance to Plasmodium falciparum in diverse anopheline species. PLoS Pathogens 5: e1000335.

7. GuptaL, Molina-CruzA, KumarS, RodriguesJ, DixitR, et al. (2009) The STAT pathway mediates late-phase immunity against Plasmodium in the mosquito Anopheles gambiae. Cell Host Microbe 5: 498–507.

8. BlandinSA, MaroisE, LevashinaEA (2008) Antimalarial responses in Anopheles gambiae: from a complement-like protein to a complement-like pathway. Cell Host Microbe 3: 364–374.

9. AbrahamE, PintoS, GhoshA, VanlandinghamDL, BuddA, et al. (2005) An immune-responsive serpin, SRPN6, mediates mosquito defense against malaria parasites. Proc Natl Acad Sci USA 102: 16327–16332.

10. PintoSB, KafatosFC, MichelK (2008) The parasite invasion marker SRPN6 reduces sporozoite numbers in salivary glands of Anopheles gambiae. Cell Microbiol 10: 891–898.

11. AbrahamEG, IslamS, SrinivasanP, GhoshAK, ValenzuelaJG, et al. (2004) Analysis of the Plasmodium and Anopheles transcriptional repertoire during ookinete development and midgut invasion. J Biol Chem 279: 5573–80.

12. KadotaK, IshinoT, MatsuyamaT, ChinzeiY, YudaM (2004) Essential role of membrane-attack protein in malarial transmission to mosquito host. Proc Natl Acad Sci USA 101: 16310–16315.

13. CirimotichCM, DongY, GarverLS, SimS, DimopoulosG (2010) Mosquito immune defenses against Plasmodium infection. Dev Comp Immunol 34: 387–395.

14. Barillas-MuryC, HanYS, SeeleyD, KafatosFC (1999) Anopheles gambiae Ag-STAT, a new insect member of the STAT family, is activated in response to bacterial infection. EMBO J 18: 959–967.

15. DongY, AguilarR, XiZ, WarrE, MonginE, et al. (2006) Anopheles gambiae immune responses to human and rodent Plasmodium parasite species. PLoS Pathogens 2: e52.

16. BaileyTL, ElkanC (2004) Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc Int Conf Intell Syst Mol Biol 2: 28–36.

17. GhoshA, EdwardsM, Jacobs-LorenaM (2000) The journey of the malaria parasite in the mosquito: hopes for the new century. Parasitol Today 16: 196–201.

18. WhittenMM, ShiaoSH, LevashinaEA (2006) Mosquito midguts and malaria: cell biology, compartmentalization and immunology. Parasite Immunol 28: 121–130.

19. MendesAM, Awono-AmbenePH, NsangoSE, CohuetA, FontenilleD, et al. (2011) Infection intensity-dependent responses of Anopheles gambiae to the African malaria parasite Plasmodium falciparum. Infect Immun 79: 4708–15.

20. DanielliA, Barillas-MuryC, KumarS, KafatosFC, LoukerisTG (2005) Overexpression and altered nucleocytoplasmic distribution of Anopheles ovalbumin-like SRPN10 serpins in Plasmodium-infected midgut cells. Cell Microbiol 7: 181–190.

21. HanYS, ThompsonJ, KafatosFC, Barillas-MuryC (2000) Molecular interactions between Anopheles stephensi midgut cells and Plasmodium berghei: the time bomb theory of ookinete invasion of mosquitoes. EMBO J 19: 6030–40.

22. KumarS, GuptaL, HanYS, Barillas-MuryC (2004) Inducible peroxidases mediate nitration of anopheles midgut cells undergoing apoptosis in response to Plasmodium invasion. J Biol Chem 279: 53475–82.

23. Oliveira GdeA, LiebermanJ, Barillas-MuryC (2012) Epithelial nitration by a peroxidase/NOX5 system mediates mosquito antiplasmodial immunity. Science 335: 856–9.

24. MichelK, BuddA, PintoS, GibsonTJ, KafatosFC (2005) Anopheles gambiae SRPN2 facilitates midgut invasion by the malaria parasite Plasmodium berghei. EMBO Rep 6: 891–7.

25. AnC, BuddA, KanostMR, MichelK (2011) Characterization of a regulatory unit that controls melanization and affects longevity of mosquitoes. Cell Mol Life Sci 68: 1929–39.

26. Franke-FayardB, TruemanH, RamesarJ, MendozaJ, KeurMVD, et al. (2004) A Plasmodium berghei reference line that constitutively expresses GFP at a high level throughout the complete life cycle. Mol Biochem Parasitol 137: 23–33.

27. LivakKJ, SchmittgenTD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402–408.

28. BaumJ, RichardD, HealerJ, RugM, KrnajskiZ, et al. (2006) A conserved molecular motor drives cell invasion and gliding motility across malaria life cycle stages and other apicomplexan parasites. J Biol Chem 281: 5197–5208.

29. BlandinS, MoitaLF, KöcherT, WilmM, KafatosFC, et al. (2002) Reverse genetics in the mosquito Anopheles gambiae: targeted disruption of the Defensin gene. EMBO Rep 3: 852–856.

30. WrightW, FunkW (1993) CASTing for multicomponent DNA-binding complexes. Trends Biochem Sci 18: 77–80.

31. GiguereV, TiniM, FlockG, OngE, EvansRM, et al. (1994) Isoform-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors. Genes Dev 8: 538–553.