Humanized mice are susceptible to Salmonella typhi infection

作     者：M Firoz Mian Elisabeth A Pek Meghan J Chenoweth Ali A Ashkar 

作者机构：Institute for Infectious Disease ResearchCentre for Gene TherapeuticsDepartment of Pathology and Molecular MedicineMcMaster UniversityHamiltonOntarioCanada 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2011年第8卷第1期

页      面：83-87页

核心收录：

学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：This study was supported by a grant from CIHR to Ali A Ashkar.AAA is a recipient of a Career Award in Health Sciences from Rx&D/CIHR. 

主　　题：animal model humanized mice RAG2-/-γc-/- Salmonella typhi 

摘      要：Salmonella enterica serovar Typhi is a pathogen that only infects humans.Currently,there is no animal model for studying this pathogen.Recently,alymphoid RAG2^(-/-)/γc^(-/-) mice engrafted with human leukocytes,known as humanized mice,have been successfully utilized to develop experimental models for several human-specific viral infections,including HIV,human-like dengue fever and hepatitis C virus.Little is known about the usefulness and feasibility of the humanized mouse model for the study of human-specific bacterial pathogens,such as S.typhi.The aim of this study was to determine if Salmonella enterica serovar Typhi could establish productive infection in humanized mice.Here we report that intravenous inoculation of S.typhi into humanized mice,but not controls,established S.typhi infections.High bacterial loads were found in the liver,spleen,blood and bone marrow of mice reconstituted with human leukocytes,but not in the unreconstituted control mice.Importantly,S.typhi-infected humanized mice lost significant body weight,and some of the infected mice displayed neurological symptoms.Our data suggest,for the first time,that humanized mice are susceptible to S.typhi challenge and that this model can be utilized to study the pathogenesis of S.typhito develop novel therapeutic strategies.