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Macrophage depletion of CMV latently infected donor hearts ameliorates recipient accelerated chronic rejection
Author(s) -
Haese Nicole N.,
Burg Jennifer M.,
Andoh Takeshi F.,
Jones Iris K. A.,
Kreklywich Craig N.,
Smith Patricia P.,
Orloff Susan L.,
Streblow Daniel N.
Publication year - 2021
Publication title -
transplant infectious disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.69
H-Index - 67
eISSN - 1399-3062
pISSN - 1398-2273
DOI - 10.1111/tid.13514
Subject(s) - medicine , chemokine , inflammation , immunology , fibrosis , transplant rejection , immune system , transplantation , macrophage , infiltration (hvac) , heart transplantation , cytomegalovirus , pathology , virus , biology , viral disease , herpesviridae , biochemistry , physics , in vitro , thermodynamics
Cytomegalovirus (CMV) infection is linked to acceleration of solid organ transplant vascular sclerosis (TVS) and chronic rejection (CR). Donor latent CMV infection increases cardiac‐resident macrophages and T cells leading to increased inflammation, promoting allograft rejection. To investigate the role of cardiac‐resident passenger macrophages in CMV‐mediated TVS/CR, macrophages were depleted from latently ratCMV (RCMV)‐infected donor allografts prior to transplantation. Latently RCMV‐infected donor F344 rats were treated with clodronate, PBS, or control liposomes 3 days prior to cardiac transplant into RCMV‐naïve Lewis recipients. Clodronate treatment significantly increased graft survival from post‐operative day (POD)61 to POD84 and decreased TVS at rejection. To determine the kinetics of the effect of clodronate treatment's effect, a time study revealed that clodronate treatment significantly decreased macrophage infiltration into allograft tissues as early as POD14; altered allograft cytokine/chemokine protein levels, fibrosis development, and inflammatory gene expression profiles. These findings support our hypothesis that increased graft survival as a result of allograft passenger macrophage depletion was in part a result of altered immune response kinetics. Depletion of donor macrophages prior to transplant is a strategy to modulate allograft rejection and reduce TVS in the setting of CMV + donors transplanted into CMV naïve recipients.