Integrative analysis associates monocytes with insufficient erythropoiesis during acute Plasmodium cynomolgi malaria in rhesus macaques

Malaria Journal

Research

Celia L. Saney¹  Stephanie Soderberg¹  Chester J. Joyner¹  Stacey A. Lapp¹  Monica Cabrera-Mora¹  Tracey J. Lamb²  Mary R. Galinski³  Suman B. Pakala⁴  Jeremy D. DeBarry⁴  Mustafa V. Nural⁵  Jessica C. Kissinger⁶  Yan Tang⁷  Mark P. Styczynski⁷ 

[1] Malaria Host–Pathogen Interaction Center, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA;Malaria Host–Pathogen Interaction Center, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA;Department of Pathology, University of Utah, Salt Lake City, UT, USA;Malaria Host–Pathogen Interaction Center, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA;Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, GA, USA;Malaria Host–Pathogen Interaction Center, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA;Institute of Bioinformatics, University of Georgia, Athens, GA, USA;Malaria Host–Pathogen Interaction Center, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA;Institute of Bioinformatics, University of Georgia, Athens, GA, USA;Department of Computer Science, University of Georgia, Athens, GA, USA;Malaria Host–Pathogen Interaction Center, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA;Institute of Bioinformatics, University of Georgia, Athens, GA, USA;Department of Genetics, University of Georgia, Athens, GA, USA;Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, USA;Department of Computer Science, University of Georgia, Athens, GA, USA;School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA;Malaria Host–Pathogen Interaction Center, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA;

关键词: Plasmodium cynomolgi;    GATA1;    Nonhuman primates;    Relapse;    Plasmodium vivax;    Bone marrow;    Erythropoiesis;    Transcriptomics;    Systems biology;    Immune response;   

DOI  :  10.1186/s12936-017-2029-z

 received in 2017-05-31, accepted in 2017-09-12,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundMild to severe anaemia is a common complication of malaria that is caused in part by insufficient erythropoiesis in the bone marrow. This study used systems biology to evaluate the transcriptional and alterations in cell populations in the bone marrow during Plasmodium cynomolgi infection of rhesus macaques (a model of Plasmodium vivax malaria) that may affect erythropoiesis.ResultsAn appropriate erythropoietic response did not occur to compensate for anaemia during acute cynomolgi malaria despite an increase in erythropoietin levels. During this period, there were significant perturbations in the bone marrow transcriptome. In contrast, relapses did not induce anaemia and minimal changes in the bone marrow transcriptome were detected. The differentially expressed genes during acute infection were primarily related to ongoing inflammatory responses with significant contributions from Type I and Type II Interferon transcriptional signatures. These were associated with increased frequency of intermediate and non-classical monocytes. Recruitment and/or expansion of these populations was correlated with a decrease in the erythroid progenitor population during acute infection, suggesting that monocyte-associated inflammation may have contributed to anaemia. The decrease in erythroid progenitors was associated with downregulation of genes regulated by GATA1 and GATA2, two master regulators of erythropoiesis, providing a potential molecular basis for these findings.ConclusionsThese data suggest the possibility that malarial anaemia may be driven by monocyte-associated disruption of GATA1/GATA2 function in erythroid progenitors resulting in insufficient erythropoiesis during acute infection.

【 授权许可】

CC BY   
© The Author(s) 2017