Innate immune responses of pulmonary epithelial cells to Burkholderia pseudomallei infection
Burkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection occurs through an infectious aerosol. Previous studies indicated that the epithelial cells in the lung are an active participant in host immunity. In thi...
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Published in | PloS one Vol. 4; no. 10; p. e7308 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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06.10.2009
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Abstract | Burkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection occurs through an infectious aerosol. Previous studies indicated that the epithelial cells in the lung are an active participant in host immunity. In this study, we aimed to investigate the innate immune responses of lung epithelial cells against B. pseudomallei.
Using a murine lung epithelial cell line, primary lung epithelial cells and an inhalational murine infection model, we characterized the types of innate immunity proteins and peptides produced upon B. pseudomallei infection. Among a wide panel of immune components studied, increased levels of major pro-inflammatory cytokines IL-6 and TNFalpha, chemokine MCP-1, and up-regulation of secretory leukocyte protease inhibitor (SLPI) and chemokine (C-C motif) ligand 20 (CCL20) were observed. Inhibition assays using specific inhibitors suggested that NF-kappaB and p38 MAPK pathways were responsible for these B. pseudomallei-induced antimicrobial peptides.
Our findings indicate that the respiratory epithelial cells, which form the majority of the cells lining the epithelial tract and the lung, have important roles in the innate immune response against B. pseudomallei infection. |
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AbstractList | Background Burkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection occurs through an infectious aerosol. Previous studies indicated that the epithelial cells in the lung are an active participant in host immunity. In this study, we aimed to investigate the innate immune responses of lung epithelial cells against B. pseudomallei. Methodology and Principal Findings Using a murine lung epithelial cell line, primary lung epithelial cells and an inhalational murine infection model, we characterized the types of innate immunity proteins and peptides produced upon B. pseudomallei infection. Among a wide panel of immune components studied, increased levels of major pro-inflammatory cytokines IL-6 and TNF[alpha], chemokine MCP-1, and up-regulation of secretory leukocyte protease inhibitor (SLPI) and chemokine (C-C motif) ligand 20 (CCL20) were observed. Inhibition assays using specific inhibitors suggested that NF-[kappa]B and p38 MAPK pathways were responsible for these B. pseudomallei-induced antimicrobial peptides. Conclusions Our findings indicate that the respiratory epithelial cells, which form the majority of the cells lining the epithelial tract and the lung, have important roles in the innate immune response against B. pseudomallei infection. BACKGROUND:Burkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection occurs through an infectious aerosol. Previous studies indicated that the epithelial cells in the lung are an active participant in host immunity. In this study, we aimed to investigate the innate immune responses of lung epithelial cells against B. pseudomallei. METHODOLOGY AND PRINCIPAL FINDINGS:Using a murine lung epithelial cell line, primary lung epithelial cells and an inhalational murine infection model, we characterized the types of innate immunity proteins and peptides produced upon B. pseudomallei infection. Among a wide panel of immune components studied, increased levels of major pro-inflammatory cytokines IL-6 and TNFalpha, chemokine MCP-1, and up-regulation of secretory leukocyte protease inhibitor (SLPI) and chemokine (C-C motif) ligand 20 (CCL20) were observed. Inhibition assays using specific inhibitors suggested that NF-kappaB and p38 MAPK pathways were responsible for these B. pseudomallei-induced antimicrobial peptides. CONCLUSIONS:Our findings indicate that the respiratory epithelial cells, which form the majority of the cells lining the epithelial tract and the lung, have important roles in the innate immune response against B. pseudomallei infection. Burkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection occurs through an infectious aerosol. Previous studies indicated that the epithelial cells in the lung are an active participant in host immunity. In this study, we aimed to investigate the innate immune responses of lung epithelial cells against B. pseudomallei. Using a murine lung epithelial cell line, primary lung epithelial cells and an inhalational murine infection model, we characterized the types of innate immunity proteins and peptides produced upon B. pseudomallei infection. Among a wide panel of immune components studied, increased levels of major pro-inflammatory cytokines IL-6 and TNF[alpha], chemokine MCP-1, and up-regulation of secretory leukocyte protease inhibitor (SLPI) and chemokine (C-C motif) ligand 20 (CCL20) were observed. Inhibition assays using specific inhibitors suggested that NF-[kappa]B and p38 MAPK pathways were responsible for these B. pseudomallei-induced antimicrobial peptides. Our findings indicate that the respiratory epithelial cells, which form the majority of the cells lining the epithelial tract and the lung, have important roles in the innate immune response against B. pseudomallei infection. Background Burkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection occurs through an infectious aerosol. Previous studies indicated that the epithelial cells in the lung are an active participant in host immunity. In this study, we aimed to investigate the innate immune responses of lung epithelial cells against B. pseudomallei. Methodology and Principal Findings Using a murine lung epithelial cell line, primary lung epithelial cells and an inhalational murine infection model, we characterized the types of innate immunity proteins and peptides produced upon B. pseudomallei infection. Among a wide panel of immune components studied, increased levels of major pro-inflammatory cytokines IL-6 and TNFα, chemokine MCP-1, and up-regulation of secretory leukocyte protease inhibitor (SLPI) and chemokine (C-C motif) ligand 20 (CCL20) were observed. Inhibition assays using specific inhibitors suggested that NF-κB and p38 MAPK pathways were responsible for these B. pseudomallei-induced antimicrobial peptides. Conclusions Our findings indicate that the respiratory epithelial cells, which form the majority of the cells lining the epithelial tract and the lung, have important roles in the innate immune response against B. pseudomallei infection. Background Burkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection occurs through an infectious aerosol. Previous studies indicated that the epithelial cells in the lung are an active participant in host immunity. In this study, we aimed to investigate the innate immune responses of lung epithelial cells against B. pseudomallei. Methodology and Principal Findings Using a murine lung epithelial cell line, primary lung epithelial cells and an inhalational murine infection model, we characterized the types of innate immunity proteins and peptides produced upon B. pseudomallei infection. Among a wide panel of immune components studied, increased levels of major pro-inflammatory cytokines IL-6 and TNFI-, chemokine MCP-1, and up-regulation of secretory leukocyte protease inhibitor (SLPI) and chemokine (C-C motif) ligand 20 (CCL20) were observed. Inhibition assays using specific inhibitors suggested that NF-IoB and p38 MAPK pathways were responsible for these B. pseudomallei-induced antimicrobial peptides. Conclusions Our findings indicate that the respiratory epithelial cells, which form the majority of the cells lining the epithelial tract and the lung, have important roles in the innate immune response against B. pseudomallei infection. BACKGROUNDBurkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection occurs through an infectious aerosol. Previous studies indicated that the epithelial cells in the lung are an active participant in host immunity. In this study, we aimed to investigate the innate immune responses of lung epithelial cells against B. pseudomallei.METHODOLOGY AND PRINCIPAL FINDINGSUsing a murine lung epithelial cell line, primary lung epithelial cells and an inhalational murine infection model, we characterized the types of innate immunity proteins and peptides produced upon B. pseudomallei infection. Among a wide panel of immune components studied, increased levels of major pro-inflammatory cytokines IL-6 and TNFalpha, chemokine MCP-1, and up-regulation of secretory leukocyte protease inhibitor (SLPI) and chemokine (C-C motif) ligand 20 (CCL20) were observed. Inhibition assays using specific inhibitors suggested that NF-kappaB and p38 MAPK pathways were responsible for these B. pseudomallei-induced antimicrobial peptides.CONCLUSIONSOur findings indicate that the respiratory epithelial cells, which form the majority of the cells lining the epithelial tract and the lung, have important roles in the innate immune response against B. pseudomallei infection. Background Burkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection occurs through an infectious aerosol. Previous studies indicated that the epithelial cells in the lung are an active participant in host immunity. In this study, we aimed to investigate the innate immune responses of lung epithelial cells against B. pseudomallei. Methodology and Principal Findings Using a murine lung epithelial cell line, primary lung epithelial cells and an inhalational murine infection model, we characterized the types of innate immunity proteins and peptides produced upon B. pseudomallei infection. Among a wide panel of immune components studied, increased levels of major pro-inflammatory cytokines IL-6 and TNFα, chemokine MCP-1, and up-regulation of secretory leukocyte protease inhibitor (SLPI) and chemokine (C-C motif) ligand 20 (CCL20) were observed. Inhibition assays using specific inhibitors suggested that NF-κB and p38 MAPK pathways were responsible for these B. pseudomallei-induced antimicrobial peptides. Conclusions Our findings indicate that the respiratory epithelial cells, which form the majority of the cells lining the epithelial tract and the lung, have important roles in the innate immune response against B. pseudomallei infection. Burkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection occurs through an infectious aerosol. Previous studies indicated that the epithelial cells in the lung are an active participant in host immunity. In this study, we aimed to investigate the innate immune responses of lung epithelial cells against B. pseudomallei. Using a murine lung epithelial cell line, primary lung epithelial cells and an inhalational murine infection model, we characterized the types of innate immunity proteins and peptides produced upon B. pseudomallei infection. Among a wide panel of immune components studied, increased levels of major pro-inflammatory cytokines IL-6 and TNFalpha, chemokine MCP-1, and up-regulation of secretory leukocyte protease inhibitor (SLPI) and chemokine (C-C motif) ligand 20 (CCL20) were observed. Inhibition assays using specific inhibitors suggested that NF-kappaB and p38 MAPK pathways were responsible for these B. pseudomallei-induced antimicrobial peptides. Our findings indicate that the respiratory epithelial cells, which form the majority of the cells lining the epithelial tract and the lung, have important roles in the innate immune response against B. pseudomallei infection. |
Audience | Academic |
Author | Thong, Tuck Weng Liu, Yichun Wang, Dongling Ooi, Eng Eong Sivalingam, Suppiah Paramalingam Novem, Vidhya Sim, Siew Hoon Tan, Gladys |
AuthorAffiliation | 2 Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore, Republic of Singapore 1 Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore, Republic of Singapore Singapore Immunology Network, Singapore |
AuthorAffiliation_xml | – name: 1 Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore, Republic of Singapore – name: 2 Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore, Republic of Singapore – name: Singapore Immunology Network, Singapore |
Author_xml | – sequence: 1 givenname: Siew Hoon surname: Sim fullname: Sim, Siew Hoon organization: Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore, Republic of Singapore – sequence: 2 givenname: Yichun surname: Liu fullname: Liu, Yichun – sequence: 3 givenname: Dongling surname: Wang fullname: Wang, Dongling – sequence: 4 givenname: Vidhya surname: Novem fullname: Novem, Vidhya – sequence: 5 givenname: Suppiah Paramalingam surname: Sivalingam fullname: Sivalingam, Suppiah Paramalingam – sequence: 6 givenname: Tuck Weng surname: Thong fullname: Thong, Tuck Weng – sequence: 7 givenname: Eng Eong surname: Ooi fullname: Ooi, Eng Eong – sequence: 8 givenname: Gladys surname: Tan fullname: Tan, Gladys |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/19806192$$D View this record in MEDLINE/PubMed |
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Copyright | COPYRIGHT 2009 Public Library of Science 2009 Sim et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Sim et al. 2009 |
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Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Conceived and designed the experiments: SHS YL SPS EEO GT. Performed the experiments: SHS DW VN SPS TWT. Analyzed the data: SHS. Wrote the paper: SHS YL EEO GT. |
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Snippet | Burkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection occurs... Background Burkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection... BACKGROUNDBurkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection... BACKGROUND:Burkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection... Background Burkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection... |
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SubjectTerms | Aerosols Analysis Animals Antimicrobial peptides Bacteria Burkholderia Infections - immunology Burkholderia Infections - metabolism Burkholderia pseudomallei Burkholderia pseudomallei - metabolism CCL20 protein Cell Line Chemokine CCL2 - metabolism Chemokines Cytokines Disseminated infection Epithelial cells Epithelial Cells - immunology Epithelial Cells - microbiology Female Gene expression Growth factors Health aspects Helicobacter pylori Immune response Immune system Immunity Immunity, Innate Immunology Immunology/Immune Response Immunology/Immunity to Infections Immunology/Innate Immunity Infection Infections Infectious Diseases/Bacterial Infections Infectious Diseases/Respiratory Infections Inflammation Innate immunity Interleukin 6 Interleukin-6 - metabolism Kinases Laboratories Lung - immunology Lung - microbiology Lungs Lymphocytes B MAP kinase Medical research Mice Mice, Inbred BALB C Mice, Inbred C57BL Monocyte chemoattractant protein 1 NF-κB protein Peptides Pneumonia Protease inhibitors Proteases Proteins Shigella Transgenic animals Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-TNF Tumor necrosis factor-α Wind |
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Title | Innate immune responses of pulmonary epithelial cells to Burkholderia pseudomallei infection |
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