title: A role for Toll-like receptor 4 in the host response to the lung infection of Yersinia pseudotuberculosis in mice.
abstract: Although a Yersinia pseudotuberculosis (Yptb) lung infection model has been developed to study Y. pestis pathogenesis, it is still necessary to establish a new animal model to mimic the pathophysiological features induced by Y. pestis infection. Here, we provide a new lung infection model using the Yptb strain, IP2777, which displayed rapid spread of bacteria to the liver, spleen, and blood. In addition, we examined whether TLR4 is involved in Yptb-induced pathogenesis in the lung infection model of mice we generated. Following lung infection of WT and TLR4-deficient mice with the Yptb strain IP2777, the survival rate, bacterial colonization, histopathology, and level of cytokines and chemokines in the lung, spleen, liver, and blood were analyzed. TLR4-deficient mice had a lower survival rate than WT mice in response to Yptb lung infection. Although the bacterial colonization and pathology of the lung were comparable between WT and TLR4-deficient mice, those of the spleen and liver were more severe in TLR4-deficient mice. In addition, the levels of TNF-α and CXCL2 in the liver and IL-6 and CXCL2 in the blood were higher in TLR4-deficient mice than in WT mice. Our results demonstrate that TLR4 is necessary for optimal host protection against Yptb lung infection and TLR4-deficient mice may serve as a better genetic model of Yptb infection for mimicking Y. pestis infection.
authors: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea.
authors: Jin-A
authors: JA
authors: Choi
authors: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea.
authors: Yu-Jin
authors: YJ
authors: Jeong
authors: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea.
authors: Jae-Eun
authors: JE
authors: Kim
authors: Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors: Min-Jung
authors: MJ
authors: Kang
authors: CBD 5th-3, Agency for Defense Development, Daejeon 305-152, Republic of Korea.
authors: Jee-Cheon
authors: JC
authors: Kim
authors: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea.
authors: Sang-Muk
authors: SM
authors: Oh
authors: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea.
authors: Kyung-Bok
authors: KB
authors: Lee
authors: University of Michigan Medical School, Department of Pathology and Comprehensive Cancer Center, Ann Arbor, MI 48109, USA.
authors: Dong-Hyun
authors: DH
authors: Kim
authors: Laboratory Animal Resource Center, Daegu Gyeongbuk Institute of Science & Technology (DGIST), Daegu 42988, South Korea. Electronic address: Kimdj77@gmail.com.
authors: Dong-Jae
authors: DJ
authors: Kim
authors: Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea. Electronic address: jonpark@jnu.ac.kr.
authors: Jong-Hwan
authors: JH
authors: Park
mesh_terms: D000818:Animals; D058491:Bacterial Load; D018925:Chemokines / Q000097:blood / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004195:Disease Models, Animal; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000382:microbiology*; D008171:Lung Diseases / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000382:microbiology; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015011:Yersinia pseudotuberculosis / Q000276:immunology* / Q000472:pathogenicity; D015012:Yersinia pseudotuberculosis Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology
chemical_list: D018925:Chemokines; D016207:Cytokines; D051197:Toll-Like Receptor 4
keywords: Lung infection; Systemic dissemination; Toll-like receptor 4; Yersinia pseudotuberculosis