Induced Pluripotent Stem Cell Derived Macrophages as a Cellular System to Study Salmonella and Other Pathogens

被引：36

作者：

Hale, Christine ^{[1
]}

Yeung, Amy ^{[1
]}

Goulding, David ^{[1
]}

Pickard, Derek ^{[1
]}

Alasoo, Kaur ^{[1
]}

Powrie, Fiona ^{[1
,2
]}

Dougan, Gordon ^{[1
]}

Mukhopadhyay, Subhankar ^{[1
,2
]}

机构：

[1] Wellcome Trust Sanger Inst, Cambridge, England

[2] Univ Oxford, Kennedy Inst Rheumatol, Oxford, England

来源：

PLOS ONE | 2015年 / 10卷 / 05期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

ENTERICA SEROVAR TYPHI; IN-VITRO; DIFFERENTIATION; RECEPTORS; RECOGNITION; EXPRESSION; IMMUNITY; VECTORS; DISEASE; MODEL;

D O I：

10.1371/journal.pone.0124307

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A number of pathogens, including several human-restricted organisms, persist and replicate within macrophages (M phi s) as a key step in pathogenesis. The mechanisms underpinning such host-restricted intracellular adaptations are poorly understood, in part, due to a lack of appropriate model systems. Here we explore the potential of human induced pluripotent stem cell derived macrophages (iPSDMs) to study such pathogen interactions. We show iPSDMs express a panel of established M phi-specific markers, produce cytokines, and polarise into classical and alternative activation states in response to IFN-gamma and IL-4 stimulation, respectively. iPSDMs also efficiently phagocytosed inactivated bacterial particles as well as live Salmonella Typhi and S. Typhimurium and were able to kill these pathogens. We conclude that iPSDMs can support productive Salmonella infection and propose this as a flexible system to study host/pathogen interactions. Furthermore, iPSDMs can provide a flexible and practical cellular platform for assessing host responses in multiple genetic backgrounds.

引用

页数：20