Sirkadiyen Ritim, İmmünite ve Enfeksiyon Hastalıkları
Özet
Biyolojik ritimler, canlıların dış dünyadaki döngüsel fiziksel etkenlere karşı gösterdikleri biyokimyasal, fizyolojik ve davranışsal yanıtları kapsar ve yaklaşık 24 saat süren döngülere sirkadiyen ritim adı verilir. Memelilerde suprakiazmatik çekirdek tarafından koordine edilen bu sistem; uyku-uyanıklık, metabolizma ve immün fonksiyonlar gibi pek çok süreci kontrol eder. Son araştırmalar, moleküler saat mekanizmasının B, T ve makrofaj gibi immün hücrelerinde de aktif olduğunu ve lökosit trafiği ile sitokin salınımı gibi süreçleri ritmik olarak yönettiğini göstermektedir. İmmün sistemin bu döngüsel çalışması, enfeksiyon durumunda konakçı savunmasını optimize etmeye ve inflamasyonun dokulara vereceği zararı en aza indirmeye yardımcı olur. Ayrıca Hepatit C, İnfluenza A, HIV, Salmonella ve Leishmania gibi viral, bakteriyel ve paraziter patojenlerin de sirkadiyen ritimlerle yakın bir etkileşim içinde olduğu ve hastalık patogenezlerinin bu saat mekanizmalarına göre değişiklik gösterdiği saptanmıştır. Sonuç olarak, immün hücrelerin ve mikroorganizmaların biyolojik saatle olan bu güçlü ilişkisinin anlaşılması, enfeksiyon hastalıklarının tanı ve tedavisinde zaman ayarlı yeni klinik yaklaşımların (kronoterapi) önünü açmaktadır.
Biological rhythms encompass biochemical, physiological, and behavioral responses of organisms to recurring physical factors, and the approximately 24-hour cycles are called circadian rhythms. Coordinated by the suprachiasmatic nucleus in mammals, this system controls various processes including sleep-wake cycles, metabolism, and immune functions. Recent research demonstrates that the molecular clock mechanism is active in immune cells such as B cells, T cells, and macrophages, rhythmically governing leukocyte trafficking and cytokine release. This cyclical operation of the immune system helps optimize host defense during infection and minimizes tissue damage caused by inflammation. Furthermore, viral, bacterial, and parasitic pathogens like Hepatitis C, Influenza A, HIV, Salmonella, and Leishmania interact closely with circadian rhythms, showing variations in disease pathogenesis based on these clock mechanisms. Consequently, understanding this robust relationship between immune cells and microorganisms with the biological clock paves the way for time-tailored clinical approaches (chronotherapy) in diagnosing and treating infectious diseases.
Referanslar
Sözlü S, Şanlıer N. Sirkadiyen ritim, sağlık ve beslenme ilişkisi. Türkiye Klinikleri Sağlık Bilimleri Dergisi. 2017; 2(2): 100-109.
Astiz M, Heyde I, and Oster H. Mechanisms of communication in the mammalian circadian timing system. International Journal of Molecular Sciences. 2019;20:343. doi.org/10.3390/ijms20020343
Borrmann H, McKeating JA, Zhuang X. The Circadian Clock and Viral Infections. Journal of Biological Rhythms. 2021;36(1):9-22. doi:10.1177/0748730420967768
Man K, Loudon A, Chawla A. Immunity around the lock. Science. 2016;354(6315):999-1003.
Bass J, Takahashi JS. Circadian Integration of Metabolism and Energetics. Science. 2010;330(6009):1349–1354.DOI: 10.1126/science.1195027
Montaruli A, Castelli L, Mulè A, et al. Biological Rhythm and Chronotype: New Perspectives in Health. Biomolecules. 2021; 11: 487. https://doi.org/ 10.3390/biom11040487
Anderson G, Reiter RJ. Melatonin: Roles in influenza, Covid-19, and other viral infections. Reviews of Medical Virology. 2020;30:e2109. https://doi.org/10.1002/rmv.2109
Takahashi JS. Transcriptional architecture of the mammalian circadian clock. Nature Reviews Genetics. 2017;18:164–179. https://doi.org/10.1038/nrg.2016.150
Partch CL, Green CB, Takahashi JS. Molecular architecture of the mammalian circadian clock. Trends in Cell Biology. 2014; 24:90–99. https://doi.org/10.1016/j.tcb.2013.07.002
Panda S, Antoch MP, Miller BH, et al. Coordinated transcription of key pathways in the mouse by the circadian clock. Cell. 2002; 109(3):307–320. https://doi.org/10.1016/S0092-8674(02)00722-5
Zhuang X, Rambhatla SB, Lai AG, et al. Interplay between circadian clock and viral infection. Journal of Molecular Medicine. 2017;95(12):1283-1289. https://doi.org/10.1007/s00109-017-1592-7
Edgar RS, Stangherlin A, Nagy AD, et al. Cell autonomous regulation of herpes and influenza virus infection by the circadian clock. Proceedings of the National Academy of Sciences. 2016;113(36):10085-10090. https://doi.org/10.1073/pnas.1601895113
Carroll RG, Timmons GA, Cervantes-Silva MP, et al. Immunometabolism around the Clock. Trends in molecular medicine. 2019;25(7):612-625. https://doi.org/10.1016/j.molmed.2019.04.013
Early JO, Curtis AM. Immunometabolism: Is it under the eye of the clock?. In Seminars in Immunology. 2016;28:478-490. https://doi.org/10.1016/j.smim.2016.10.006
Halberg F, Johnson EA, Brown BW, et al. Susceptibility rhythm to E. coli endotoxin and bioassay. Proceedings of the Society for Experimental Biology and Medicine. 1960;103(1):142-144. https://doi.org/10.3181/00379727-103-25439
Alamili M, Bendtzen K, Lykkesfeldt J, et al. Pronounced Inflammatory Response to Endotoxaemia during Nighttime: A Randomised Cross-Over Trial. PLOS ONE. 2014;9(1):e87413. https://doi.org/10.1371/journal.pone.0087413
Castanon-Cervantes O, Wu M, Ehlen JC, et al. Dysregulation of inflammatory responses by chronic circadian disruption. The Journal of Immunology. 2010;185(10):5796-5805. https://doi.org/10.4049/jimmunol.1001026
Cuesta M, Boudreau P, Dubeau-Laramée G, et al. Simulated night shift disrupts circadian rhythms of immune functions in humans. The Journal of Immunology. 2016;196(6):2466-2475. https://doi.org/10.4049/jimmunol.1502422
Haus E, Smolensky MH. Biologic rhythms in the immune system. Chronobıology Internatıonal. 1999;16(5):581–622. https://doi.org/10.3109/07420529908998730
Waggoner SN. Circadian Rhythms in Immunity. Current Allergy and Asthma Reports. 2020;20:2. https://doi.org/10.1007/s11882-020-0896-9
Sun Y, Yang Z, Niu Z, et al. MOP3, a component of the molecular clock, regulates the development of B cells. Immunology. 2006;119(4):451-60. https://doi.org/10.1111/j.1365-2567.2006.02456.x
Hemmers S, Rudensky AY. The cell-intrinsic circadian clock is dispensable for lymphocyte differentiation and function. Cell Reports. 2015;11(9):1339-49. https://doi.org/10.1016/j.celrep.2015.04.058
Nguyen KD, Fentress SJ, Qiu Y, et al. Circadian gene Bmal1 regulates diurnal oscillations of Ly6C(hi) inflammatory monocytes. Science. 2013;341(6153):1483–8. DOI:10.1126/science.1240636
Casanova-Acebes M, Pitaval C, Weiss LA, et al. Rhythmic modulation of the hematopoietic niche through neutrophil clearance. Cell. 2013;153(5):1025–35. https://doi.org/10.1016/j.cell.2013.04.040
Mendez-Ferrer S, Lucas D, Battista M, et al. Haematopoietic stem cell release is regulated by circadian oscillations. Nature. 2008; 452(7186): 442–7. https://doi.org/10.1038/nature06685
Haspel JA, Chettimada S, Shaik R, et al. Circadian rhythm reprogramming during lung inflammation. Nature Communications. 2014; 5:4753.
Gibbs J, Ince L, Matthews L, et al. An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action. Nature Medicine. 2014;20(8):919–26. https://doi.org/10.1038/nm.3599
Shimba A, Cui G, Tani-ichi S, et al. Glucocorticoids Drive Diurnal Oscillations in T Cell Distribution and Responses by Inducing Interleukin-7 Receptor and CXCR4. Immunity. 2018;48(2):286–298. https://doi.org/10.1016/j.immuni.2018.01.004
Druzd D, Matveeva O, Ince L et al. Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses. Immunity. 2017;46(1):120–32. https://doi.org/10.1016/j.immuni.2016.12.011
Adrover JM, Del Fresno C, Crainiciuc G, et al. A Neutrophil Timer Coordinates Immune Defense and Vascular Protection. Immunity. 2019; 50(2): 390–402. https://doi.org/10.1016/j.immuni.2019.01.002
Medzhitov, R. Origin and physiological roles of inflammation. Nature. 2008; 454: 428–435. https://doi.org/10.1038/nature07201
Okin D, Medzhitov R. Evolution of Inflammatory Diseases. Current Biology. 2012;22(17):733–740. https://doi.org/10.1016/j.cub.2012.07.029
Nguyen KD, Fentress SJ, Qiu Y, et al. Circadian gene Bmal1 regulates diurnal oscillations of Ly6Chi inflammatory monocytes. Science. 2013;341(6153):1483-1488.DOI: 10.1126/science.1240636
Narasimamurthy R, Hatori M, Nayak SK, et al. Circadian clock protein cryptochrome regulates the expression of proinflammatory cytokines. Proceedings of the National Academy of Sciences of the United States of America. 2012; 109(31): 12662-12667. https://doi.org/10.1073/pnas.1209965109
Spengler ML, Kuropatwinski KK, Comas M, et al. Core circadian protein CLOCK is a positive regulator of NF-κB–mediated transcription. Proceedings of the National Academy of Sciences of the United States of America. 2012;109:E245-E2465. https://doi.org/10.1073/pnas.1206274109
Fang B, Lazar MA. Dissecting the Rev-erba Cistrome and the Mechanisms Controlling Circadian Transcription in Liver. Cold Spring Harbor Symposia on Quantitative Biology. 2015; 80:233–238. Doi:10.1101/sqb.2015.80.027508
Lam M, Cho H, Lesch H, et al. Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription. Nature.2013;498: 511–515. https://doi.org/10.1038/nature12209
Eichenfield DZ, Troutman TD, Link VM, et al. Tissue damage drives co-localization of NF-κB, Smad3, and Nrf2 to direct Rev-erb sensitive wound repair in mouse macrophages. eLife.2016;5: e13024. DOI:10.7554/eLife.13024
Keller M, Mazuch J, Abraham U, et al. A circadian clock in macrophages controls inflammatory immune responses. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(50):21407-21412. DOI: 10.1073/pnas.0906361106
Gibbs JE, Blaikley J, Beesley S, et al. The nuclear receptor REV-ERBα mediates circadian regulation of innate immunity through selective regulation of inflammatory cytokines. Proceedings of the National Academy of Sciences of the United States of America. 2012;109:582-587. DOI: 10.1073/pnas.1106750109
Voigt RM, Forsyth CB, Green SJ, et al. Circadian rhythm and the gut microbiome. International review of neurobiology. 2016; 131:193-205. https://doi.org/10.1016/bs.irn.2016.07.002
Tognini P, Murakami M, Sassone-Corsi P. Interplay between microbes and the circadian clock. Cold Spring Harbor Perspectives in Biology. 2018;10(9):a028365. doi: 10.1101/cshperspect.a028365
Cohen SE, Golden SS. Circadian rhythms in cyanobacteria. Microbiology and Molecular Biology Reviews. 2015;79(4):373-385. https://doi.org/10.1128/MMBR.00036-15
Mazzoccoli G, Vinciguerra M, Carbone A, et al. The Circadian Clock, the Immune System, and Viral Infections: The Intricate Relationship Between Biological Time and Host-Virus Interaction. Pathogens. 2020;9(2):83. https://doi.org/10.3390/pathogens9020083
Zhuang X, Magri A, Hill M, et al. The circadian clock components BMAL1 and REV-ERBalpha regulate flavivirus replication. Nature Communications. 2019;10(1):377. https://doi.org/10.1038/s41467-019-08299-7
Benegiamo G, Mazzoccoli G, Cappello F, et al. Mutual antagonism between circadian protein period 2 and hepatitis C virus replication in hepatocytes. PloS one. 2013; 8(4): e60527. https://doi.org/10.1371/journal.pone.0060527
Bellet MM, Masri S, Astarita G, et al. Histone deacetylase sirt1 controls proliferation, circadian rhythm, and lipid metabolism during liver regeneration in mice. Journal of Biological Chemistry. 2016;291:23318–23329. DOI:https://doi.org/10.1074/jbc.M116.737114
Sato S, Solanas G, Peixoto FO, et al. Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging. Cell. 2017; 170:664e11–677e11. https://doi.org/10.1016/j.cell.2017.07.042
Sengupta S, Tang SY, Devine JC, et al. Circadian control of lung inflammation in influenza infection. Nature Communications. 2019;10(1):4107. https://doi.org/10.1038/s41467-019-11400-9
Zhang Z, Hunter L, Wu G, et al. Genome‐wide effect of pulmonary airway epithelial cell‐specific bmal1 deletion. The FASEB Journal. 2019;33:6226–6238. https://doi.org/10.1096/fj.201801682R
Clark III JP, Sampair CS, Kofuji P, et al. HIV protein, transactivator of transcription, alters circadian rhythms through the light entrainment pathway. American Journal of Physiology Regulatory, Integrative and Comparative Physiology. 2005; 289(3):R656-R662. https://doi.org/10.1152/ajpregu.00179.2005
Nath A, Psooy K, Martin C, et al. Identification of a human immunodeficiency virus type 1 Tat epitope that is neuroexcitatory and neurotoxic. Journal of Virology. 1996;70: 1475–1480.
Majumdar T, Dhar J, Patel S, et al. Circadian transcription factor BMAL1 regulates innate immunity against select RNA viruses. Innate Immunity. 2017;23(2):147–54. https://doi.org/10.1177/1753425916681075
Tan DX, Korkmaz A, Reiter RJ, et al. Ebola virus disease: potential use of melatonin as a treatment. Journal of Pineal Research. 2014; 57: 381–384. https://doi.org/10.1111/jpi.12186
Bellet MM, Deriu E, Liu JZ, et al. Circadian clock regulates the host response to Salmonella. Proceedings of the National Academy of Sciences of the United States of America. 2013;110: 9897–9902. https://doi.org/10.1073/pnas.1120636110
Nguyen KD, Fentress SJ, Qiu Y, et al. Circadian gene Bmal1 regulates diurnal oscillations of Ly6Chi inflammatory monocytes. Science. 2013;341:1483-1488.DOI: 10.1126/science.1240636
Carvalho Cabral P, Olivier M, Cermakian N. The complex interplay of parasites, their hosts, and circadian clocks. Frontiers in Cellular and Infection Microbiology. 2019; 9: 425. Doi: 10.3389/fcimb.2019.00425
Hunter FK, Butler TD, Gibbs JE. Circadian rhythms in immunity and host‐parasite interactions. Parasite Immunology. 2022; e12904. https://doi.org/10.1111/pim.12904
Rijo-Ferreira F, Pinto-Neves D, Barbosa-Morais NL, et al. Trypanosoma brucei metabolism is under circadian control. Nature Microbiology. 2017;2:17032. https://doi.org/10.1038/nmicrobiol.2017.32
Prior KF, van der Veen DR, O’Donnell AJ, et al. Timing of host feeding drives rhythms in parasite replication. PLoS pathogens. 2018; 14(2):e1006900. https://doi.org/10.1371/journal.ppat.1006900
