Skip to main content

Murine CMV induces type 1 IFN that impairs differentiation of MDSCs critical for transplantation tolerance.

Publication ,  Journal Article
Dangi, A; Zhang, L; Zhang, X; Luo, X
Published in: Blood Adv
March 27, 2018

Clinical tolerance without immunosuppression has now been achieved for organ transplantation, and its scope will likely continue to expand. In this context, a previously understudied and now increasingly relevant area is how microbial infections might affect the efficacy of tolerance. A highly prevalent and clinically relevant posttransplant pathogen is cytomegalovirus (CMV). Its impact on transplantation tolerance and graft outcomes is not well defined. Employing a mouse model of CMV (MCMV) infection and allogeneic pancreatic islet transplantation in which donor-specific tolerance was induced by infusing donor splenocytes rendered apoptotic by treatment with ethylenecarbodiimide, we investigated the effect of CMV infection on transplantation tolerance induction. We found that acute MCMV infection abrogated tolerance induction and that this abrogation correlated with an alteration in the differentiation and function of myeloid-derived suppressor cells (MDSCs). These effects on MDSCs were mediated in part through MCMV induced type 1 interferon (IFN) production. During MCMV infection, the highly immunosuppressive Gr1HI-granulocytic MDSCs were markedly reduced in numbers, and the accumulating Ly6CHI-monocytic cells lost their MDSC-like function but instead acquired an immunostimulatory phenotype to cross-present alloantigens and prime alloreactive CD8 T cells. Consequently, the islet allograft exhibited an altered effector to regulatory T-cell ratio that correlated with the ultimate graft demise. Blocking type 1 IFN signaling during MCMV infection rescued MDSC populations and partially restored transplantation tolerance. Our mechanistic studies now provide a solid foundation for seeking effective therapies for promoting transplantation tolerance in settings of CMV infection.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Blood Adv

DOI

EISSN

2473-9537

Publication Date

March 27, 2018

Volume

2

Issue

6

Start / End Page

669 / 680

Location

United States

Related Subject Headings

  • Virus Replication
  • Transplantation Tolerance
  • T-Lymphocyte Subsets
  • Myeloid-Derived Suppressor Cells
  • Muromegalovirus
  • Monocytes
  • Mice
  • Male
  • Islets of Langerhans
  • Interferon Type I
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Dangi, A., Zhang, L., Zhang, X., & Luo, X. (2018). Murine CMV induces type 1 IFN that impairs differentiation of MDSCs critical for transplantation tolerance. Blood Adv, 2(6), 669–680. https://doi.org/10.1182/bloodadvances.2017012187
Dangi, Anil, Lei Zhang, Xiaomin Zhang, and Xunrong Luo. “Murine CMV induces type 1 IFN that impairs differentiation of MDSCs critical for transplantation tolerance.Blood Adv 2, no. 6 (March 27, 2018): 669–80. https://doi.org/10.1182/bloodadvances.2017012187.
Dangi A, Zhang L, Zhang X, Luo X. Murine CMV induces type 1 IFN that impairs differentiation of MDSCs critical for transplantation tolerance. Blood Adv. 2018 Mar 27;2(6):669–80.
Dangi, Anil, et al. “Murine CMV induces type 1 IFN that impairs differentiation of MDSCs critical for transplantation tolerance.Blood Adv, vol. 2, no. 6, Mar. 2018, pp. 669–80. Pubmed, doi:10.1182/bloodadvances.2017012187.
Dangi A, Zhang L, Zhang X, Luo X. Murine CMV induces type 1 IFN that impairs differentiation of MDSCs critical for transplantation tolerance. Blood Adv. 2018 Mar 27;2(6):669–680.

Published In

Blood Adv

DOI

EISSN

2473-9537

Publication Date

March 27, 2018

Volume

2

Issue

6

Start / End Page

669 / 680

Location

United States

Related Subject Headings

  • Virus Replication
  • Transplantation Tolerance
  • T-Lymphocyte Subsets
  • Myeloid-Derived Suppressor Cells
  • Muromegalovirus
  • Monocytes
  • Mice
  • Male
  • Islets of Langerhans
  • Interferon Type I