#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

How the Fly Balances Its Ability to Combat Different Pathogens


Health is a multidimensional landscape. If we just consider the host, there are many outputs that interest us: evolutionary fitness determining parameters like fecundity, survival and pathogen clearance as well as medically important health parameters like sleep, energy stores and appetite. Hosts use a variety of effector pathways to fight infections and these effectors are brought to bear differentially. Each pathogen causes a different disease as they have distinct virulence factors and niches; they each warp the health landscape in unique ways. Therefore, mutations affecting immunity can have complex phenotypes and distinct effects on each pathogen. Here we describe how two components of the fly's immune response, melanization and phagocytosis, contribute to the health landscape generated by the transcription factor ets21c (CG2914) and its putative effector, the signaling molecule wntD (CG8458). To probe the landscape, we infect with two pathogens: Listeria monocytogenes, which primarily lives intracellularly, and Streptococcus pneumoniae, which is an extracellular pathogen. Using the diversity of phenotypes generated by these mutants, we propose that survival during a L. monocytogenes infection is mediated by a combination of two host mechanisms: phagocytic activity and melanization; while survival during a S. pneumoniae infection is determined by phagocytic activity. In addition, increased phagocytic activity is beneficial during S. pneumoniae infection but detrimental during L. monocytogenes infection, demonstrating an inherent trade-off in the immune response.


Vyšlo v časopise: How the Fly Balances Its Ability to Combat Different Pathogens. PLoS Pathog 8(12): e32767. doi:10.1371/journal.ppat.1002970
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002970

Souhrn

Health is a multidimensional landscape. If we just consider the host, there are many outputs that interest us: evolutionary fitness determining parameters like fecundity, survival and pathogen clearance as well as medically important health parameters like sleep, energy stores and appetite. Hosts use a variety of effector pathways to fight infections and these effectors are brought to bear differentially. Each pathogen causes a different disease as they have distinct virulence factors and niches; they each warp the health landscape in unique ways. Therefore, mutations affecting immunity can have complex phenotypes and distinct effects on each pathogen. Here we describe how two components of the fly's immune response, melanization and phagocytosis, contribute to the health landscape generated by the transcription factor ets21c (CG2914) and its putative effector, the signaling molecule wntD (CG8458). To probe the landscape, we infect with two pathogens: Listeria monocytogenes, which primarily lives intracellularly, and Streptococcus pneumoniae, which is an extracellular pathogen. Using the diversity of phenotypes generated by these mutants, we propose that survival during a L. monocytogenes infection is mediated by a combination of two host mechanisms: phagocytic activity and melanization; while survival during a S. pneumoniae infection is determined by phagocytic activity. In addition, increased phagocytic activity is beneficial during S. pneumoniae infection but detrimental during L. monocytogenes infection, demonstrating an inherent trade-off in the immune response.


Zdroje

1. Shirasu-HizaMM, DionneMS, PhamLN, AyresJS, SchneiderDS (2007) Interactions between circadian rhythm and immunity in Drosophila melanogaster. Curr Biol 17: R353–355.

2. AyresJS, SchneiderDS (2009) The role of anorexia in resistance and tolerance to infections in Drosophila. PLoS Biol 7: e1000150.

3. DionneMS, PhamLN, Shirasu-HizaM, SchneiderDS (2006) Akt and FOXO dysregulation contribute to infection-induced wasting in Drosophila. Curr Biol 16: 1977–1985.

4. AyresJS, SchneiderDS (2008) A signaling protease required for melanization in Drosophila affects resistance and tolerance of infections. PLoS Biol 6: 2764–2773.

5. HaineER, MoretY, Siva-JothyMT, RolffJ (2008) Antimicrobial defense and persistent infection in insects. Science 322: 1257–1259.

6. StoneEF, FultonBO, AyresJS, PhamLN, ZiauddinJ, et al. (2012) The circadian clock protein timeless regulates phagocytosis of bacteria in Drosophila. PLoS Pathog 8: e1002445.

7. NehmeNT, QuintinJ, ChoJH, LeeJ, LafargeMC, et al. (2011) Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections. PLoS One 6: e14743.

8. HashimotoY, TabuchiY, SakuraiK, KutsunaM, KurokawaK, et al. (2009) Identification of lipoteichoic acid as a ligand for draper in the phagocytosis of Staphylococcus aureus by Drosophila hemocytes. J Immunol 183: 7451–7460.

9. Elrod-EricksonM, MishraS, SchneiderD (2000) Interactions between the cellular and humoral immune responses in Drosophila. Curr Biol 10: 781–784.

10. TangH (2009) Regulation and function of the melanization reaction in Drosophila. Fly (Austin) 3: 105–111.

11. ZhaoP, LuZ, StrandMR, JiangH (2011) Antiviral, anti-parasitic, and cytotoxic effects of 5,6-dihydroxyindole (DHI), a reactive compound generated by phenoloxidase during insect immune response. Insect Biochem Mol Biol 41: 645–652.

12. GanesanS, AggarwalK, PaquetteN, SilvermanN (2011) NF-kappaB/Rel proteins and the humoral immune responses of Drosophila melanogaster. Curr Top Microbiol Immunol 349: 25–60.

13. AgaisseH (2008) Investigating the involvement of host factors involved in intracellular pathogen infection by RNAi in Drosophila cells. Methods Mol Biol 415: 395–402.

14. AgaisseH, BurrackLS, PhilipsJA, RubinEJ, PerrimonN, et al. (2005) Genome-wide RNAi screen for host factors required for intracellular bacterial infection. Science 309: 1248–1251.

15. MansfieldBE, DionneMS, SchneiderDS, FreitagNE (2003) Exploration of host-pathogen interactions using Listeria monocytogenes and Drosophila melanogaster. Cell Microbiol 5: 901–911.

16. PhamLN, DionneMS, Shirasu-HizaM, SchneiderDS (2007) A specific primed immune response in Drosophila is dependent on phagocytes. PLoS Pathog 3: e26.

17. AyresJS, FreitagN, SchneiderDS (2008) Identification of Drosophila mutants altering defense of and endurance to Listeria monocytogenes infection. Genetics 178: 1807–1815.

18. RadyukSN, MichalakK, KlichkoVI, BenesJ, OrrWC (2010) Peroxiredoxin 5 modulates immune response in Drosophila. Biochim Biophys Acta 1800: 1153–1163.

19. JohanssonKC, MetzendorfC, SoderhallK (2005) Microarray analysis of immune challenged Drosophila hemocytes. Exp Cell Res 305: 145–155.

20. GordonMD, DionneMS, SchneiderDS, NusseR (2005) WntD is a feedback inhibitor of Dorsal/NF-kappaB in Drosophila development and immunity. Nature 437: 746–749.

21. GordonMD, AyresJS, SchneiderDS, NusseR (2008) Pathogenesis of listeria-infected Drosophila wntD mutants is associated with elevated levels of the novel immunity gene edin. PLoS Pathog 4: e1000111.

22. SchneiderDS, AyresJS, BrandtSM, CostaA, DionneMS, et al. (2007) Drosophila eiger mutants are sensitive to extracellular pathogens. PLoS Pathog 3: e41.

23. ChengLW, VialaJP, StuurmanN, WiedemannU, ValeRD, et al. (2005) Use of RNA interference in Drosophila S2 cells to identify host pathways controlling compartmentalization of an intracellular pathogen. Proc Natl Acad Sci U S A 102: 13646–13651.

24. ChengLW, PortnoyDA (2003) Drosophila S2 cells: an alternative infection model for Listeria monocytogenes. Cell Microbiol 5: 875–885.

25. TzouP, ReichhartJM, LemaitreB (2002) Constitutive expression of a single antimicrobial peptide can restore wild-type resistance to infection in immunodeficient Drosophila mutants. Proc Natl Acad Sci U S A 99: 2152–2157.

26. SchneiderD, ShahabuddinM (2000) Malaria parasite development in a Drosophila model. Science 288: 2376–2379.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2012 Číslo 12
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#