title: A species-specific activation of Toll-like receptor signaling in bovine and sheep bronchial epithelial cells triggered by Mycobacterial infections.
abstract: Pulmonary tuberculosis caused by a Mycobacterium infection remains a major public health problem in most part of the world, in part owing to the transmission of its pathogens between hosts including human, domestic and wild animals. To date, molecular mechanisms of the pathogenesis of TB are still incompletely understood. In addition to alveolar macrophages, airway epithelial cells have also been recently recognized as main targets for Mycobacteria infections. In an effort to understand the pathogen-host interaction between Mycobacteria and airway epithelial cells in domestic animals, in present study, we investigated the Toll-like receptor (TLR) signaling in bovine and sheep airway epithelial cells in response to an infection of Mycobacterium tuberculosis avirulent H37Ra stain or Mycobacterium bovis BCG vaccine strain, using primary air-liquid interface (ALI) bronchial epithelial culture models. Our results revealed a host and pathogen species-specific TLR-mediated recognition of pathogen-associated molecular patterns (PAMPs), induction and activation of TLR signaling pathways, and substantial induction of inflammatory response in bronchial epithelial cells in response to Mycobacteria infections between these two species. Interestingly, the activation TLR signaling in bovine bronchial epithelial cells induced by Mycobacteria infection was mainly through a myeloid differentiation factor 88 (MyD88)-independent TLR signaling pathway, while both MyD88-dependent and independent TLR signaling cascades could be induced in sheep epithelial cells. Equally noteworthy, a BCG infection was able to induce both MyD88-dependent and independent signaling in sheep and bovine airway epithelial cells, but more robust inflammatory responses were induced in sheep epithelial cells relative to the bovines; whereas an H37Ra infection displayed an ability to mainly trigger a MyD88-independent TLR signaling cascade in these two host species, and induce a more extent expression of inflammatory cytokines in bovine cells in comparison with that in sheep. These data thus provide an evidence for a host and pathogen species-specific response in bovine and sheep airway epithelial cells in response to Mycobacteria infections, which also suggest there is a need to consider in the interpretation of data generated using a species other than the primary host for analysis of a function role or mechanism of ligands or pathogens.
authors.affiliation: Ningxia Key laboratory of Clinical and Pathogenic Microbiology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China; Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Ningxia University, Yinchuan, Ningxia 750021, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Laboratory Medicine, College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Han
authors.affiliation: Ningxia Key laboratory of Clinical and Pathogenic Microbiology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China; Department of Microbiology and Immunology, School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Liang
authors.affiliation: Ningxia Key laboratory of Clinical and Pathogenic Microbiology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Yang
authors.affiliation: Ningxia Key laboratory of Clinical and Pathogenic Microbiology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Shi
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Ningxia University, Yinchuan, Ningxia 750021, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.affiliation: The Center of Experimental Animals, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Ningxia University, Yinchuan, Ningxia 750021, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Ningxia Key laboratory of Clinical and Pathogenic Microbiology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Meihui
authors.initials: M
authors.lastname: Luo
authors.affiliation: Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Ningxia University, Yinchuan, Ningxia 750021, China.
authors.forename: Yujiong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Ningxia Key laboratory of Clinical and Pathogenic Microbiology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China; Institute of Human Stem Cell Research, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China. Electronic address: weijun@nxmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.affiliation: Ningxia Key laboratory of Clinical and Pathogenic Microbiology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China; Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, Ningxia University, Yinchuan, Ningxia 750021, China; Institute of Human Stem Cell Research, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China. Electronic address: liuxiaoming@nxmu.edu.cn.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001980:Bronchi / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002417:Cattle; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D008854:Microscopy, Electron; D009163:Mycobacterium bovis; D060888:Real-Time Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D012756:Sheep; D015398:Signal Transduction / Q000276:immunology*; D013045:Species Specificity; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000378:metabolism
chemical_list: D051193:Toll-Like Receptors
keywords: Airway epithelial cells; Bovine; Mycobacterium infection; Sheep; Species-specific recognition; Toll-like receptor signaling