Human Monocytes - CD14, CD16 - Ziegler-Heitbrock

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Case of yellow fever vaccine--associated viscerotropic disease with prolonged viremia, robust adaptive immune responses, and polymorphisms in CCR5 and RANTES genes.

Abstract

BACKGROUND: The live attenuated yellow fever vaccine 17D (YF-17D) is one of the most effective vaccines. Despite its excellent safety record, some cases of viscerotropic adverse events develop, which are sometimes fatal. The mechanisms underlying such events remain a mystery. Here, we present an analysis of the immunologic and genetic factors driving disease in a 64-year-old male who developed viscerotropic symptoms. METHODS: We obtained clinical, serologic, virologic, immunologic and genetic data on this case patient. RESULTS: Viral RNA was detected in the blood 33 days after vaccination, in contrast to the expected clearance of virus by day 7 after vaccination in healthy vaccinees. Vaccination induced robust antigen-specific T and B cell responses, which suggested that persistent virus was not due to adaptive immunity of suboptimal magnitude. The genes encoding OAS1, OAS2, TLR3, and DC-SIGN, which mediate antiviral innate immunity, were wild type. However, there were heterozygous genetic polymorphisms in chemokine receptor CCR5, and its ligand RANTES, which influence the migration of effector T cells and CD14+CD16bright monocytes to tissues. Consistent with this, there was a 200-fold increase in the number of CD14+CD16bright monocytes in the blood during viremia and even several months after virus clearance. CONCLUSION: In this patient, viscerotropic disease was not due to the impaired magnitude of adaptive immunity but instead to anomalies in the innate immune system and a possible disruption of the CCR5-RANTES axis.

Authors: Pulendran B, Miller J, Querec TD, Akondy R, Moseley N, Laur O, Glidewell J, Monson N, Zhu T, Zhu H, Staprans S, Lee D, Brinton MA, Perelygin AA, Vellozzi C, Brachman P Jr, Lalor S, Teuwen D, Eidex RB, Cetron M, Priddy F, del Rio C, Altman J, Ahmed R.
Journal: J Infect Dis. 198(4):500-7.
Year: 2008
PubMed: Find in PubMed