Activation of IFN-γ/STAT/IRF-1 in Hepatic Responses to Klebsiella pneumoniae Infection

Klebsiella pneumoniae-caused liver abscess (KLA) has become a health problem in Taiwan and is continually reported in other countries. Diabetes mellitus, the most common metabolic disorder, underlies half of the KLA patients in Taiwan. The clinical impact of KLA has been well-documented. Nevertheles...

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Published inPloS one Vol. 8; no. 11; p. e79961
Main Authors Lin, Yi-Chun, Lu, Min-Chi, Lin, Chingju, Chiang, Ming-Ko, Jan, Ming-Shiou, Tang, Hui-Ling, Liu, Hsu-Chung, Lin, Wea-Lung, Huang, Chih-Yang, Chen, Chuan-Mu, Lai, Yi-Chyi
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 06.11.2013
Public Library of Science (PLoS)
Subjects
Activation
Age
Agricultural biotechnology
Animals
Apoptosis
Bioluminescence
Caspase
Caspase 3 - metabolism
Caspase-3
Cell cycle
Chemokine CXCL2 - metabolism
Cytokines
Diabetes
Diabetes mellitus
E coli
Endoplasmic reticulum
Escherichia coli
Hepatocytes
Hospitals
IL-1β
Immunology
Infections
Infectious diseases
Insulin
Interferon
Interferon regulatory factor
Interferon regulatory factor 1
Interferon Regulatory Factor-1 - metabolism
Interferon-gamma - metabolism
Interleukin-1beta - metabolism
Internal medicine
Intestine
Klebsiella
Klebsiella Infections - metabolism
Klebsiella pneumoniae
Klebsiella pneumoniae - pathogenicity
Leukocytes (neutrophilic)
Life sciences
Liver
Liver - metabolism
Male
Medicine
Meningitis
Metabolic disorders
Metastasis
Mice
Mice, Inbred BALB C
Morbidity
Neutrophils
Organs
Pathogenesis
Physiology
Pneumonia
Proteins
Rodents
Signaling
Transcription factors
Transducers
Translocation
γ-Interferon
China
Taiwan
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Abstract Klebsiella pneumoniae-caused liver abscess (KLA) has become a health problem in Taiwan and is continually reported in other countries. Diabetes mellitus, the most common metabolic disorder, underlies half of the KLA patients in Taiwan. The clinical impact of KLA has been well-documented. Nevertheless, the molecular basis regarding how K. pneumoniae causes liver infection, particularly in diabetic individuals, remains unclear. Auto-bioluminescence-expressing K. pneumoniae was inoculated into diabetic mice and age-match naïve control. With the use of in vivo imaging system, translocation of the bioluminescence-expressing K. pneumoniae from intestine to extraintestinal organs, mainly the liver, was noted in 80% of the diabetic mice, whereas the same bacteria causes extraintestinal infections in only 31% of naïve mice. Besides increased morbidity, the severity of hepatic tissue injury was also enhanced in the K. pneumoniae-infected diabetic mice. Upon K. pneumoniae infection, IFN-γ production was significantly evoked in the liver. To mediate IFN-γ signal, STAT (signal transducers and activators of transcription) 1 and 3 were activated in hepatocytes, and so was the expression of IRF (interferon regulatory factor)-1. Moreover, accumulation of neutrophils which was triggered by prolonged production of IL-1β and MIP-2, and significant increases in the level of active caspase 3 and phospho-eIF2α, were exclusively revealed in the K. pneumoniae-infected diabetic mice. The activation of IFN-γ/STAT/IRF-1 signaling demonstrated by this work emphasizes the role of IFN-γ for mediating the hepatic response to K. pneumoniae infection.
AbstractList BACKGROUND: Klebsiella pneumoniae-caused liver abscess (KLA) has become a health problem in Taiwan and is continually reported in other countries. Diabetes mellitus, the most common metabolic disorder, underlies half of the KLA patients in Taiwan. The clinical impact of KLA has been well-documented. Nevertheless, the molecular basis regarding how K. pneumoniae causes liver infection, particularly in diabetic individuals, remains unclear. METHODOLOGY/PRINCIPLE FINDINGS: Auto-bioluminescence-expressing K. pneumoniae was inoculated into diabetic mice and age-match naïve control. With the use of in vivo imaging system, translocation of the bioluminescence-expressing K. pneumoniae from intestine to extraintestinal organs, mainly the liver, was noted in 80% of the diabetic mice, whereas the same bacteria causes extraintestinal infections in only 31% of naïve mice. Besides increased morbidity, the severity of hepatic tissue injury was also enhanced in the K. pneumoniae-infected diabetic mice. Upon K. pneumoniae infection, IFN-γ production was significantly evoked in the liver. To mediate IFN-γ signal, STAT (signal transducers and activators of transcription) 1 and 3 were activated in hepatocytes, and so was the expression of IRF (interferon regulatory factor)-1. Moreover, accumulation of neutrophils which was triggered by prolonged production of IL-1β and MIP-2, and significant increases in the level of active caspase 3 and phospho-eIF2α, were exclusively revealed in the K. pneumoniae-infected diabetic mice. CONCLUSION: The activation of IFN-γ/STAT/IRF-1 signaling demonstrated by this work emphasizes the role of IFN-γ for mediating the hepatic response to K. pneumoniae infection.
Klebsiella pneumoniae-caused liver abscess (KLA) has become a health problem in Taiwan and is continually reported in other countries. Diabetes mellitus, the most common metabolic disorder, underlies half of the KLA patients in Taiwan. The clinical impact of KLA has been well-documented. Nevertheless, the molecular basis regarding how K. pneumoniae causes liver infection, particularly in diabetic individuals, remains unclear. Auto-bioluminescence-expressing K. pneumoniae was inoculated into diabetic mice and age-match naïve control. With the use of in vivo imaging system, translocation of the bioluminescence-expressing K. pneumoniae from intestine to extraintestinal organs, mainly the liver, was noted in 80% of the diabetic mice, whereas the same bacteria causes extraintestinal infections in only 31% of naïve mice. Besides increased morbidity, the severity of hepatic tissue injury was also enhanced in the K. pneumoniae-infected diabetic mice. Upon K. pneumoniae infection, IFN-γ production was significantly evoked in the liver. To mediate IFN-γ signal, STAT (signal transducers and activators of transcription) 1 and 3 were activated in hepatocytes, and so was the expression of IRF (interferon regulatory factor)-1. Moreover, accumulation of neutrophils which was triggered by prolonged production of IL-1β and MIP-2, and significant increases in the level of active caspase 3 and phospho-eIF2α, were exclusively revealed in the K. pneumoniae-infected diabetic mice. The activation of IFN-γ/STAT/IRF-1 signaling demonstrated by this work emphasizes the role of IFN-γ for mediating the hepatic response to K. pneumoniae infection.
Klebsiella pneumoniae-caused liver abscess (KLA) has become a health problem in Taiwan and is continually reported in other countries. Diabetes mellitus, the most common metabolic disorder, underlies half of the KLA patients in Taiwan. The clinical impact of KLA has been well-documented. Nevertheless, the molecular basis regarding how K. pneumoniae causes liver infection, particularly in diabetic individuals, remains unclear.BACKGROUNDKlebsiella pneumoniae-caused liver abscess (KLA) has become a health problem in Taiwan and is continually reported in other countries. Diabetes mellitus, the most common metabolic disorder, underlies half of the KLA patients in Taiwan. The clinical impact of KLA has been well-documented. Nevertheless, the molecular basis regarding how K. pneumoniae causes liver infection, particularly in diabetic individuals, remains unclear.Auto-bioluminescence-expressing K. pneumoniae was inoculated into diabetic mice and age-match naïve control. With the use of in vivo imaging system, translocation of the bioluminescence-expressing K. pneumoniae from intestine to extraintestinal organs, mainly the liver, was noted in 80% of the diabetic mice, whereas the same bacteria causes extraintestinal infections in only 31% of naïve mice. Besides increased morbidity, the severity of hepatic tissue injury was also enhanced in the K. pneumoniae-infected diabetic mice. Upon K. pneumoniae infection, IFN-γ production was significantly evoked in the liver. To mediate IFN-γ signal, STAT (signal transducers and activators of transcription) 1 and 3 were activated in hepatocytes, and so was the expression of IRF (interferon regulatory factor)-1. Moreover, accumulation of neutrophils which was triggered by prolonged production of IL-1β and MIP-2, and significant increases in the level of active caspase 3 and phospho-eIF2α, were exclusively revealed in the K. pneumoniae-infected diabetic mice.METHODOLOGY/PRINCIPLE FINDINGSAuto-bioluminescence-expressing K. pneumoniae was inoculated into diabetic mice and age-match naïve control. With the use of in vivo imaging system, translocation of the bioluminescence-expressing K. pneumoniae from intestine to extraintestinal organs, mainly the liver, was noted in 80% of the diabetic mice, whereas the same bacteria causes extraintestinal infections in only 31% of naïve mice. Besides increased morbidity, the severity of hepatic tissue injury was also enhanced in the K. pneumoniae-infected diabetic mice. Upon K. pneumoniae infection, IFN-γ production was significantly evoked in the liver. To mediate IFN-γ signal, STAT (signal transducers and activators of transcription) 1 and 3 were activated in hepatocytes, and so was the expression of IRF (interferon regulatory factor)-1. Moreover, accumulation of neutrophils which was triggered by prolonged production of IL-1β and MIP-2, and significant increases in the level of active caspase 3 and phospho-eIF2α, were exclusively revealed in the K. pneumoniae-infected diabetic mice.The activation of IFN-γ/STAT/IRF-1 signaling demonstrated by this work emphasizes the role of IFN-γ for mediating the hepatic response to K. pneumoniae infection.CONCLUSIONThe activation of IFN-γ/STAT/IRF-1 signaling demonstrated by this work emphasizes the role of IFN-γ for mediating the hepatic response to K. pneumoniae infection.
Background Klebsiella pneumoniae -caused liver abscess (KLA) has become a health problem in Taiwan and is continually reported in other countries. Diabetes mellitus, the most common metabolic disorder, underlies half of the KLA patients in Taiwan. The clinical impact of KLA has been well-documented. Nevertheless, the molecular basis regarding how K. pneumoniae causes liver infection, particularly in diabetic individuals, remains unclear. Methodology/Principle Findings Auto-bioluminescence-expressing K. pneumoniae was inoculated into diabetic mice and age-match naïve control. With the use of in vivo imaging system, translocation of the bioluminescence-expressing K. pneumoniae from intestine to extraintestinal organs, mainly the liver, was noted in 80% of the diabetic mice, whereas the same bacteria causes extraintestinal infections in only 31% of naïve mice. Besides increased morbidity, the severity of hepatic tissue injury was also enhanced in the K. pneumoniae -infected diabetic mice. Upon K. pneumoniae infection, IFN-γ production was significantly evoked in the liver. To mediate IFN-γ signal, STAT (signal transducers and activators of transcription) 1 and 3 were activated in hepatocytes, and so was the expression of IRF (interferon regulatory factor)-1. Moreover, accumulation of neutrophils which was triggered by prolonged production of IL-1β and MIP-2, and significant increases in the level of active caspase 3 and phospho-eIF2α, were exclusively revealed in the K. pneumoniae -infected diabetic mice. Conclusion The activation of IFN-γ/STAT/IRF-1 signaling demonstrated by this work emphasizes the role of IFN-γ for mediating the hepatic response to K. pneumoniae infection.
Author Huang, Chih-Yang
Lu, Min-Chi
Jan, Ming-Shiou
Lin, Wea-Lung
Lai, Yi-Chyi
Lin, Yi-Chun
Lin, Chingju
Liu, Hsu-Chung
Chiang, Ming-Ko
Tang, Hui-Ling
Chen, Chuan-Mu
AuthorAffiliation 5 Department of Physiology, School of Medicine, China Medical University, Taichung, Taiwan
4 Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan
1 Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan
2 Division of Infectious Diseases, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
8 Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
7 Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan
14 Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan
9 School of Medicine, Chung Shan Medical University, Taichung, Taiwan
3 Department of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan
13 Graduate Institute of Basic Medical Science Chinese Medical Science, China Medical University, Taichung, Taiwan
6
AuthorAffiliation_xml – name: 14 Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/24223208$$D View this record in MEDLINE/PubMed
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Conceived and designed the experiments: Y.C. Lai MCL CMC Y.C. Lin. Performed the experiments: Y.C. Lai HLT HCL. Analyzed the data: Y.C. Lai CYH CL WLL MKC MSJ. Contributed reagents/materials/analysis tools: MSJ. Wrote the manuscript: Y.C. Lai MCL CMC.
Competing Interests: The authors have declared that no competing interests exist.
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Snippet Klebsiella pneumoniae-caused liver abscess (KLA) has become a health problem in Taiwan and is continually reported in other countries. Diabetes mellitus, the...
Background Klebsiella pneumoniae-caused liver abscess (KLA) has become a health problem in Taiwan and is continually reported in other countries. Diabetes...
BACKGROUND: Klebsiella pneumoniae-caused liver abscess (KLA) has become a health problem in Taiwan and is continually reported in other countries. Diabetes...
Background Klebsiella pneumoniae -caused liver abscess (KLA) has become a health problem in Taiwan and is continually reported in other countries. Diabetes...
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StartPage e79961
SubjectTerms Activation
Age
Agricultural biotechnology
Animals
Apoptosis
Bioluminescence
Caspase
Caspase 3 - metabolism
Caspase-3
Cell cycle
Chemokine CXCL2 - metabolism
Cytokines
Diabetes
Diabetes mellitus
E coli
Endoplasmic reticulum
Escherichia coli
Hepatocytes
Hospitals
IL-1β
Immunology
Infections
Infectious diseases
Insulin
Interferon
Interferon regulatory factor
Interferon regulatory factor 1
Interferon Regulatory Factor-1 - metabolism
Interferon-gamma - metabolism
Interleukin-1beta - metabolism
Internal medicine
Intestine
Klebsiella
Klebsiella Infections - metabolism
Klebsiella pneumoniae
Klebsiella pneumoniae - pathogenicity
Leukocytes (neutrophilic)
Life sciences
Liver
Liver - metabolism
Male
Medicine
Meningitis
Metabolic disorders
Metastasis
Mice
Mice, Inbred BALB C
Morbidity
Neutrophils
Organs
Pathogenesis
Physiology
Pneumonia
Proteins
Rodents
Signaling
Transcription factors
Transducers
Translocation
γ-Interferon
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Title Activation of IFN-γ/STAT/IRF-1 in Hepatic Responses to Klebsiella pneumoniae Infection
URI https://www.ncbi.nlm.nih.gov/pubmed/24223208
https://www.proquest.com/docview/1458280781
https://www.proquest.com/docview/1458504714
https://pubmed.ncbi.nlm.nih.gov/PMC3819302
https://doaj.org/article/e2871f1eb736448487553cadbff2292f
http://dx.doi.org/10.1371/journal.pone.0079961
Volume 8
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