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Cytomegalovirus (CMV) is an immunomodulatory virus that indirectly increases the risk for bacterial, fungal, and viral infections. However, the pathogenesis of this phenomenon is poorly understood. We determined whether inflammatory responses to different Toll-like receptor (TLR) ligands are blunted during CMV infection in solid-organ transplant (SOT) patients. Peripheral blood mononuclear cells from 38 SOT patients with and without CMV were incubated in the presence of various viral, fungal, and bacterial TLR ligands. Cytokines were measured in the supernatant by multiplex enzyme-linked immunosorbent assay. Patients had blunted cytokine responses to bacterial, fungal, and viral ligands during CMV infection when compared to the absence of CMV infection. This was independent of viral load, clinical presentation of CMV infection or immunosuppression, supporting the clinical observation in SOT recipients that CMV infection increases susceptibility to bacterial, fungal, and other viral infections. Moreover, in the absence of CMV infection, patients with subsequent CMV infection had lower cytokines in response to TLR ligands compared to those without subsequent CMV infection, suggesting that inherent differences in patients not directly related to CMV also contribute to this increased susceptibility. In summary, these data provide novel ex vivo evidence to support indirect effects of CMV.

Titel:	Improving our mechanistic understanding of the indirect effects of CMV infection in transplant recipients.
Autor/in / Beteiligte Person:	L'Huillier, AG ; Ferreira, VH ; Ku, T ; Bahinskaya, I ; Kumar, D ; Humar, A
Link:	Full Text Finder (Volltext)
Zeitschrift:	American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Jg. 19 (2019-09-01), Heft 9, S. 2495-2504
Veröffentlichung:	2023- : [New York] : Elsevier ; <i>Original Publication</i>: Copenhagen : Munksgaard International Publishers, 2001-, 2019
Medientyp:	academicJournal
ISSN:	1600-6143 (electronic)
DOI:	10.1111/ajt.15371
Schlagwort:	Adult Antiviral Agents therapeutic use Cytokines metabolism Cytomegalovirus Female Ganciclovir therapeutic use Humans Immunosuppression Therapy adverse effects Inflammation immunology Leukocytes, Mononuclear cytology Ligands Male Middle Aged Organ Transplantation Pilot Projects Postoperative Complications Prospective Studies Valganciclovir therapeutic use Viral Load Cytomegalovirus Infections complications Inflammation metabolism Toll-Like Receptors metabolism Transplant Recipients Transplantation adverse effects
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Am J Transplant] 2019 Sep; Vol. 19 (9), pp. 2495-2504. <i>Date of Electronic Publication: </i>2019 Apr 23. MeSH Terms: Transplant Recipients* ; Cytomegalovirus Infections / complications ; Inflammation / metabolism ; Toll-Like Receptors / metabolism ; Transplantation / adverse effects ; Adult ; Antiviral Agents / therapeutic use ; Cytokines / metabolism ; Cytomegalovirus ; Female ; Ganciclovir / therapeutic use ; Humans ; Immunosuppression Therapy / adverse effects ; Inflammation / immunology ; Leukocytes, Mononuclear / cytology ; Ligands ; Male ; Middle Aged ; Organ Transplantation ; Pilot Projects ; Postoperative Complications ; Prospective Studies ; Valganciclovir / therapeutic use ; Viral Load References: Kotton CN, Kumar D, Caliendo AM, et al. Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation. 2013;96(4):333-360. ; Gorensek MJ, Stewart RW, Keys TF, et al. Symptomatic cytomegalovirus infection as a significant risk factor for major infections after cardiac transplantation. J Infect Dis. 1988;158(4):884-887. ; George MJ, Snydman DR, Werner BG, et al. The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG-Study Group. Cytogam, MedImmune, Inc. Gaithersburg, Maryland. Am J Med. 1997;103(2):106-113. ; Husni RN, Gordon SM, Longworth DL, et al. Cytomegalovirus infection is a risk factor for invasive aspergillosis in lung transplant recipients. Clin Infect Dis. 1998;26(3):753-755. ; Peterson PK, Balfour HH Jr, Marker SC, et al. Cytomegalovirus disease in renal allograft recipients: a prospective study of the clinical features, risk factors and impact on renal transplantation. Medicine (Baltimore). 1980;59(4):283-300. ; Collins LA, Samore MH, Roberts MS, et al. Risk factors for invasive fungal infections complicating orthotopic liver transplantation. J Infect Dis. 1994;170(3):644-652. ; Falagas ME, Snydman DR, Griffith J et al. Exposure to cytomegalovirus from the donated organ is a risk factor for bacteremia in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG Study Group. Clin Infect Dis. 1996;23(3):468-474. ; Paya CV, Wiesner RH, Hermans PE, et al. Risk factors for cytomegalovirus and severe bacterial infections following liver transplantation: a prospective multivariate time-dependent analysis. J Hepatol. 1993;18(2):185-195. ; Linares L, Sanclemente G, Cervera C, et al. Influence of cytomegalovirus disease in outcome of solid organ transplant patients. Transplant Proc. 2011;43(6):2145-2148. ; Manez R, Breinig MK, Linden P, et al. Factors associated with the development of post-transplant lymphoproliferative disease (PTLD) in Epstein-Barr virus (EBV)-seronegative adult liver transplant recipients. Transpl Int. 1994;7(Suppl 1):S235-S237. ; Bosch W, Heckman MG, Pungpapong S, et al. Association of cytomegalovirus infection and disease with recurrent hepatitis C after liver transplantation. Transplantation. 2012;93(7):723-728. ; Montoya JG, Giraldo LF, Efron B, et al. Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center. Clin Infect Dis. 2001;33(5):629-640. ; Lowance D, Neumayer HH, Legendre CM, et al. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group. N Engl J Med. 1999;340(19):1462-1470. ; Wagner JA, Ross H, Hunt S, et al. Prophylactic ganciclovir treatment reduces fungal as well as cytomegalovirus infections after heart transplantation. Transplantation. 1995;60(12):1473-1477. ; Munoz-Price LS, Slifkin M, Ruthazer R, et al. The clinical impact of ganciclovir prophylaxis on the occurrence of bacteremia in orthotopic liver transplant recipients. Clin Infect Dis. 2004;39(9):1293-1299. ; Kalil AC, Levitsky J, Lyden E, et al. Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients. Ann Intern Med. 2005;143(12):870-880. ; Hodson EM, Jones CA, Webster AC, et al. Antiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomised controlled trials. Lancet. 2005;365(9477):2105-2115. ; O'Neill LA, Bryant CE, Doyle SL. Therapeutic targeting of toll-like receptors for infectious and inflammatory diseases and cancer. Pharmacol Rev. 2009;61(2):177-197. ; Mifsud EJ, Tan AC, Jackson DC. TLR agonists as modulators of the innate immune response and their potential as agents against infectious disease. Front Immunol. 2014;5:79. ; Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004;4(7):499-511. ; Ida JA, Shrestha N, Desai S, et al. A whole blood assay to assess peripheral blood dendritic cell function in response to Toll-like receptor stimulation. J Immunol Methods. 2006;310(1-2):86-99. ; Renn CN, Sanchez DJ, Ochoa MT, et al. TLR activation of Langerhans cell-like dendritic cells triggers an antiviral immune response. J Immunol. 2006;177(1):298-305. ; Compton T, Kurt-Jones EA, Boehme KW, et al. Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2. J Virol. 2003;77(8):4588-4596. ; Kotton CN, Kumar D, Caliendo AM, et al. The third international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation. 2018;102(6):900-931. ; Humar A, Michaels M. American Society of Transplantation recommendations for screening, monitoring and reporting of infectious complications in immunosuppression trials in recipients of organ transplantation. Am J Transplant. 2006;6(2):262-274. ; Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;49(1):1-45. ; McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):e1-e48. ; Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the infectious diseases society of America. Clin Infect Dis. 2016;63(4):e1-e60. ; Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice guidelines by the infectious diseases society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenza. Clin Infect Dis. 2018;68:e1-e47. ; Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America. Clin Infect Dis. 2016;62(4):e1-e50. ; Babicki S, Arndt D, Marcu A, et al. Heatmapper: web-enabled heat mapping for all. Nucleic Acids Res. 2016;44(W1):W147-W153. ; Rand KH, Pollard RB, Merigan TC. Increased pulmonary superinfections in cardiac-transplant patients undergoing primary cytomegalovirus infection. N Engl J Med. 1978;298(17):951-953. ; Chatterjee SN, Fiala M, Weiner J, et al. Primary cytomegalovirus and opportunistic infections. Incidence in renal transplant recipients. JAMA. 1978;240(22):2446-2449. ; Walker RC, Marshall WF, Strickler JG, et al. Pretransplantation assessment of the risk of lymphoproliferative disorder. Clin Infect Dis. 1995;20(5):1346-1353. ; Schrier RD, Oldstone MB. Recent clinical isolates of cytomegalovirus suppress human cytomegalovirus-specific human leukocyte antigen-restricted cytotoxic T-lymphocyte activity. J Virol. 1986;59(1):127-131. ; Kapasi K, Rice GP. Role of the monocyte in cytomegalovirus-mediated immunosuppression in vitro. J Infect Dis. 1986;154(5):881-884. ; Schrier RD, Rice GP, Oldstone MB. Suppression of natural killer cell activity and T cell proliferation by fresh isolates of human cytomegalovirus. J Infect Dis. 1986;153(6):1084-1091. ; Hertel L, Lacaille VG, Strobl H, et al. Susceptibility of immature and mature Langerhans cell-type dendritic cells to infection and immunomodulation by human cytomegalovirus. J Virol. 2003;77(13):7563-7574. ; Lee AW, Hertel L, Louie RK, et al. Human cytomegalovirus alters localization of MHC class II and dendrite morphology in mature Langerhans cells. J Immunol. 2006;177(6):3960-3971. ; Gredmark S, Tilburgs T, Soderberg-Naucler C. Human cytomegalovirus inhibits cytokine-induced macrophage differentiation. J Virol. 2004;78(19):10378-10389. ; Gredmark S, Soderberg-Naucler C. Human cytomegalovirus inhibits differentiation of monocytes into dendritic cells with the consequence of depressed immunological functions. J Virol. 2003;77(20):10943-10956. ; Frascaroli G, Varani S, Moepps B, et al. Human cytomegalovirus subverts the functions of monocytes, impairing chemokine-mediated migration and leukocyte recruitment. J Virol. 2006;80(15):7578-7589. ; Varani S, Frascaroli G, Homman-Loudiyi M, et al. Human cytomegalovirus inhibits the migration of immature dendritic cells by down-regulating cell-surface CCR53 and CCR53. J Leukoc Biol. 2005;77(2):219-228. ; Beck K, Meyer-Konig U, Weidmann M, et al. Human cytomegalovirus impairs dendritic cell function: a novel mechanism of human cytomegalovirus immune escape. Eur J Immunol. 2003;33(6):1528-1538. ; Frascaroli G, Varani S, Blankenhorn N, et al. Human cytomegalovirus paralyzes macrophage motility through down-regulation of chemokine receptors, reorganization of the cytoskeleton, and release of macrophage migration inhibitory factor. J Immunol. 2009;182(1):477-488. ; Hancock MH, Hook LM, Mitchell J, et al. Human cytomegalovirus microRNAs miR-US5-1 and miR-UL112-3p block proinflammatory cytokine production in response to NF-kappaB-activating factors through direct downregulation of IKKalpha and IKKbeta. MBio. 2017;8(2):e00109-e00117. ; Mathers C, Schafer X, Martinez-Sobrido L, et al. The human cytomegalovirus UL26 protein antagonizes NF-kappaB activation. J Virol. 2014;88(24):14289-14300. ; Landais I, Pelton C, Streblow D, et al. Human cytomegalovirus miR-UL112-3p Targets TLR2 and modulates the TLR2/IRAK1/NFkappaB signaling pathway. PLoS Pathog. 2015;11(5):e1004881. ; Abate DA, Watanabe S, Mocarski ES. Major human cytomegalovirus structural protein pp65 (ppUL83) prevents interferon response factor 3 activation in the interferon response. J Virol. 2004;78(20):10995-11006. ; Choi HJ, Park A, Kang S, et al. Human cytomegalovirus-encoded US9 targets MAVS and STING signaling to evade type I interferon immune responses. Nat Commun. 2018;9(1):125. ; Bowden RA, Digel J, Reed EC, et al. Immunosuppressive effects of ganciclovir on in vitro lymphocyte responses. J Infect Dis. 1987;156(6):899-903. Contributed Indexing: Keywords: cellular biology; complication: infectious; cytokines/cytokine receptors; immunobiology; infection and infectious agents - viral: Cytomegalovirus (CMV); infectious disease; innate immunity; translational research/science Substance Nomenclature: 0 (Antiviral Agents) ; 0 (Cytokines) ; 0 (Ligands) ; 0 (Toll-Like Receptors) ; GCU97FKN3R (Valganciclovir) ; P9G3CKZ4P5 (Ganciclovir) Entry Date(s): Date Created: 20190328 Date Completed: 20200923 Latest Revision: 20230124 Update Code: 20231215

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Improving our mechanistic understanding of the indirect effects of CMV infection in transplant recipients.