Autophagy Controls BCG-Induced Trained Immunity and the Response to Intravesical BCG Therapy for Bladder Cancer

English version České info

Next to its effects against tuberculosis, BCG vaccination also induces non-specific beneficial effects on immune cells to increase their ability to control unrelated pathogens. It has been recently proposed that the non-specific effects of BCG are mediated through epigenetic reprogramming of monocytes, a process called trained immunity. Little is known regarding the intracellular events controlling its induction. In this study we identified autophagy as a key player in trained immunity. Pharmacological inhibition of autophagy as well as polymorphisms in autophagy-related genes blocked BCG-induced trained immunity. Furthermore, BCG vaccine is also used to treat bladder cancer. Genetic polymorphisms in autophagy-related genes correlated with progression and recurrence of bladder cancer after treatment with BCG therapy. These findings open new possibilities for improvement of future BCG-based vaccines to be used against infections and malignancies.

Vyšlo v časopise: Autophagy Controls BCG-Induced Trained Immunity and the Response to Intravesical BCG Therapy for Bladder Cancer. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004485
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004485

Souhrn

Zdroje

1. DurrantWE, DongX (2004) Systemic acquired resistance. Annu Rev Phytopathol 42: 185–209.

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

3. SunJC, BeilkeJN, LanierLL (2009) Adaptive immune features of natural killer cells. Nature 457: 557–561.

4. O'LearyJG, GoodarziM, DraytonDL, von AndrianUH (2006) T cell- and B cell-independent adaptive immunity mediated by natural killer cells. Nat Immunol 7: 507–516.

5. NeteaMG, QuintinJ, van der MeerJW (2011) Trained immunity: a memory for innate host defense. Cell Host Microbe 9: 355–361.

6. QuintinJ, SaeedS, MartensJH, Giamarellos-BourboulisEJ, IfrimDC, et al. (2012) Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe 12: 223–232.

7. KleinnijenhuisJ, QuintinJ, PreijersF, JoostenLA, IfrimDC, et al. (2012) Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A 109: 17537–17542.

8. HusnjakK, DikicI (2012) Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions. Annu Rev Biochem 81: 291–322.

9. JagannathC, LindseyDR, DhandayuthapaniS, XuY, HunterRLJr, et al. (2009) Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells. Nat Med 15: 267–276.

10. MinY, XuW, LiuD, ShenS, LuY, et al. (2010) Autophagy promotes BCG-induced maturation of human dendritic cells. Acta Biochim Biophys Sin (Shanghai) 42: 177–182.

11. VelikkakathAK, NishimuraT, OitaE, IshiharaN, MizushimaN (2012) Mammalian Atg2 proteins are essential for autophagosome formation and important for regulation of size and distribution of lipid droplets. Mol Biol Cell 23: 896–909.

12. KawaiK, MiyazakiJ, JorakuA, NishiyamaH, AkazaH (2013) Bacillus Calmette-Guerin (BCG) immunotherapy for bladder cancer: current understanding and perspectives on engineered BCG vaccine. Cancer Sci 104: 22–27.

13. FosterSL, HargreavesDC, MedzhitovR (2007) Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 447: 972–978.

14. TrunzBB, FineP, DyeC (2006) Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness. Lancet 367: 1173–1180.

15. LevineMI, SackettMF (1946) Results of BCG immunization in New York City. Am Rev Tuberc 53: 517–532.

16. AronsonJD (1948) Protective vaccination against tuberculosis, with special reference to BCG vaccine. Minn Med 31: 1336.

17. FergusonRG, SimesAB (1949) BCG vaccination of Indian infants in Saskatchewan. Tubercle 30: 5–11.

18. VelemaJP, AlihonouEM, GandahoT, HounyeFH (1991) Childhood mortality among users and non-users of primary health care in a rural west African community. Int J Epidemiol 20: 474–479.

19. NiobeyFM, DuchiadeMP, VasconcelosAG, de CarvalhoML, Leal MdoC, et al. (1992) [Risk factors for death caused by pneumonia in children younger than 1 year old in a metropolitan region of southeastern Brazil. A case- control study]. Rev Saude Publica 26: 229–238.

20. KristensenI, AabyP, JensenH (2000) Routine vaccinations and child survival: follow up study in Guinea-Bissau, West Africa. BMJ 321: 1435–1438.

21. GarlyML, MartinsCL, BaleC, BaldeMA, HedegaardKL, et al. (2003) BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa. A non-specific beneficial effect of BCG? Vaccine 21: 2782–2790.

22. VaugeladeJ, PinchinatS, GuiellaG, ElgueroE, SimondonF (2004) Non-specific effects of vaccination on child survival: prospective cohort study in Burkina Faso. BMJ 329: 1309.

23. AabyP, RothA, RavnH, NapirnaBM, RodriguesA, et al. (2011) Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period? J Infect Dis 204: 245–252.

24. Biering-SorensenS, AabyP, NapirnaBM, RothA, RavnH, et al. (2012) Small randomized trial among low-birth-weight children receiving bacillus Calmette-Guerin vaccination at first health center contact. Pediatr Infect Dis J 31: 306–308.

25. HershEM, GuttermanJU, MavligitGM (1977) BCG as adjuvant immunotherapy for neoplasia. Annu Rev Med 28: 489–515.

26. IfrimDC, QuintinJ, JoostenLA, JacobsC, JansenT, et al. (2014) Trained immunity or tolerance: opposing functional programs induced in human monocytes after engagement of various pattern recognition receptors. Clin Vaccine Immunol 21: 534–545.

27. RafnarT, VermeulenSH, SulemP, ThorleifssonG, AbenKK, et al. (2011) European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene. Hum Mol Genet 20: 4268–4281.

28. SonganeM, KleinnijenhuisJ, AlisjahbanaB, SahiratmadjaE, ParwatiI, et al. (2012) Polymorphisms in autophagy genes and susceptibility to tuberculosis. PLoS One 7: e41618.

29. SmeekensSP, NgA, KumarV, JohnsonMD, PlantingaTS, et al. (2013) Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans. Nat Commun 4: 1342.