Ganciclovir Transiently Attenuates Murine Cytomegalovirus-associated Renal Allograft Inflammation

Overview

Journal Transplantation

Specialty General Surgery

Date 2011 Sep 1

PMID 21878840

Citations 3

Authors

Masako Shimamura

Ute Saunders

Brian Rha

Lingling Guo

Kevin A Cassady

James F George

William J Britt

Affiliations

Soon will be listed here.

Abstract

Background: Prophylactic ganciclovir (GCV) is used in high-risk renal transplant patients to prevent acute cytomegalovirus (CMV) disease, but its impact on inflammation within the allograft itself remains undefined.

Methods: To study the effect of GCV prophylaxis on allograft inflammation, murine CMV (MCMV)-infected allografts were analyzed in a murine donor positive/recipient negative allogeneic renal transplantation model by flow cytometry and immunofluorescent staining.

Results: By flow cytometry, CD45+ leukocyte infiltrates were more abundant in MCMV-infected allografts at 14 days posttransplant compared with uninfected grafts (P<0.01) and decreased in the presence of GCV (P<0.05). CD11c+ dendritic cells, Gr-1+ myeloid cells, CD204+ macrophages, and CD49b+ natural killer cells were reduced in GCV-treated allografts compared with MCMV-infected grafts without GCV treatment (P<0.05). However, GCV failed to reduce these cell types to levels found in MCMV-uninfected allografts. By day 7 after cessation of GCV prophylaxis, dendritic cells, macrophages, and natural killer cells increased in number and became statistically indistinguishable from numbers of cells found in MCMV-infected allografts without GCV. GCV treatment did not affect the numbers of CD4+, CD8+, or CD19+/B220+ lymphocytes infiltrating the allografts. Infiltrates were confirmed histologically by immunofluorescent staining for CD3+ and CD11b+ cells.

Conclusions: In this model, MCMV-infected allografts developed significantly greater innate and adaptive leukocytic infiltrates compared with uninfected grafts. GCV attenuated the MCMV-associated innate leukocyte infiltrates in infected allografts but not the lymphocytic infiltrates. The attenuated innate response was limited to the period of GCV prophylaxis.

Citing Articles

Murine cytomegalovirus promotes renal allograft inflammation via Th1/17 cells and IL-17A.

Dhital R, Anand S, Graber B, Zeng Q, Velazquez V, Boddeda S Am J Transplant. 2022; 22(10):2306-2322.

PMID: 35671112 PMC: 9547825. DOI: 10.1111/ajt.17116.

NK cell and Th17 responses are differentially induced in murine cytomegalovirus infected renal allografts and vary according to recipient virus dose and strain.

Li M, Boddeda S, Chen B, Zeng Q, Schoeb T, Velazquez V Am J Transplant. 2018; 18(11):2647-2662.

PMID: 29659179 PMC: 6191363. DOI: 10.1111/ajt.14868.

Ganciclovir prophylaxis improves late murine cytomegalovirus-induced renal allograft damage.

Shimamura M, Seleme M, Guo L, Saunders U, Schoeb T, George J Transplantation. 2012; 95(1):48-53.

PMID: 23232367 PMC: 3700407. DOI: 10.1097/TP.0b013e3182782efc.

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