Phagocytosis is a primary determinant of pulmonary clearance of clinical Klebsiella pneumoniae isolates
IntroductionKlebsiella pneumoniae (Kp) is a common cause of hospital-acquired pneumonia. Although previous studies have suggested that evasion of phagocytic uptake is a virulence determinant of Kp, few studies have examined phagocytosis sensitivity in clinical Kp isolates.MethodsWe screened 19 clini...
Ausführliche Beschreibung
Autor*in: |
Rick van der Geest [verfasserIn] Hongye Fan [verfasserIn] Hernán F. Peñaloza [verfasserIn] William G. Bain [verfasserIn] Zeyu Xiong [verfasserIn] Naina Kohli [verfasserIn] Emily Larson [verfasserIn] Mara L. G. Sullivan [verfasserIn] Jonathan M. Franks [verfasserIn] Donna B. Stolz [verfasserIn] Ryota Ito [verfasserIn] Kong Chen [verfasserIn] Yohei Doi [verfasserIn] Melanie J. Harriff [verfasserIn] Janet S. Lee [verfasserIn] |
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E-Artikel |
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Englisch |
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2023 |
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In: Frontiers in Cellular and Infection Microbiology - Frontiers Media S.A., 2016, 13(2023) |
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volume:13 ; year:2023 |
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DOI / URN: |
10.3389/fcimb.2023.1150658 |
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Katalog-ID: |
DOAJ087486245 |
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520 | |a IntroductionKlebsiella pneumoniae (Kp) is a common cause of hospital-acquired pneumonia. Although previous studies have suggested that evasion of phagocytic uptake is a virulence determinant of Kp, few studies have examined phagocytosis sensitivity in clinical Kp isolates.MethodsWe screened 19 clinical respiratory Kp isolates that were previously assessed for mucoviscosity for their sensitivity to macrophage phagocytic uptake, and evaluated phagocytosis as a functional correlate of in vivo Kp pathogenicity.ResultsThe respiratory Kp isolates displayed heterogeneity in the susceptibility to macrophage phagocytic uptake, with 14 out of 19 Kp isolates displaying relative phagocytosis-sensitivity compared to the reference Kp strain ATCC 43816, and 5 out of 19 Kp isolates displaying relative phagocytosis-resistance. Intratracheal infection with the non-mucoviscous phagocytosis-sensitive isolate S17 resulted in a significantly lower bacterial burden compared to infection with the mucoviscous phagocytosis-resistant isolate W42. In addition, infection with S17 was associated with a reduced inflammatory response, including reduced bronchoalveolar lavage fluid (BAL) polymorphonuclear (PMN) cell count, and reduced BAL TNF, IL-1β, and IL-12p40 levels. Importantly, host control of infection with the phagocytosis-sensitive S17 isolate was impaired in alveolar macrophage (AM)-depleted mice, whereas AM-depletion had no significant impact on host defense against infection with the phagocytosis-resistant W42 isolate.ConclusionAltogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical Kp isolates. | ||
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653 | 0 | |a Microbiology | |
700 | 0 | |a Hongye Fan |e verfasserin |4 aut | |
700 | 0 | |a Hernán F. Peñaloza |e verfasserin |4 aut | |
700 | 0 | |a William G. Bain |e verfasserin |4 aut | |
700 | 0 | |a William G. Bain |e verfasserin |4 aut | |
700 | 0 | |a Zeyu Xiong |e verfasserin |4 aut | |
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700 | 0 | |a Mara L. G. Sullivan |e verfasserin |4 aut | |
700 | 0 | |a Jonathan M. Franks |e verfasserin |4 aut | |
700 | 0 | |a Donna B. Stolz |e verfasserin |4 aut | |
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700 | 0 | |a Janet S. Lee |e verfasserin |4 aut | |
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10.3389/fcimb.2023.1150658 doi (DE-627)DOAJ087486245 (DE-599)DOAJd52c265d2f874b8fa7c45a112a78d396 DE-627 ger DE-627 rakwb eng QR1-502 Rick van der Geest verfasserin aut Phagocytosis is a primary determinant of pulmonary clearance of clinical Klebsiella pneumoniae isolates 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionKlebsiella pneumoniae (Kp) is a common cause of hospital-acquired pneumonia. Although previous studies have suggested that evasion of phagocytic uptake is a virulence determinant of Kp, few studies have examined phagocytosis sensitivity in clinical Kp isolates.MethodsWe screened 19 clinical respiratory Kp isolates that were previously assessed for mucoviscosity for their sensitivity to macrophage phagocytic uptake, and evaluated phagocytosis as a functional correlate of in vivo Kp pathogenicity.ResultsThe respiratory Kp isolates displayed heterogeneity in the susceptibility to macrophage phagocytic uptake, with 14 out of 19 Kp isolates displaying relative phagocytosis-sensitivity compared to the reference Kp strain ATCC 43816, and 5 out of 19 Kp isolates displaying relative phagocytosis-resistance. Intratracheal infection with the non-mucoviscous phagocytosis-sensitive isolate S17 resulted in a significantly lower bacterial burden compared to infection with the mucoviscous phagocytosis-resistant isolate W42. In addition, infection with S17 was associated with a reduced inflammatory response, including reduced bronchoalveolar lavage fluid (BAL) polymorphonuclear (PMN) cell count, and reduced BAL TNF, IL-1β, and IL-12p40 levels. Importantly, host control of infection with the phagocytosis-sensitive S17 isolate was impaired in alveolar macrophage (AM)-depleted mice, whereas AM-depletion had no significant impact on host defense against infection with the phagocytosis-resistant W42 isolate.ConclusionAltogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical Kp isolates. respiratory infection host defense Klebsiella pneumoniae phagocytosis clinical isolates macrophages Microbiology Hongye Fan verfasserin aut Hernán F. Peñaloza verfasserin aut William G. Bain verfasserin aut William G. Bain verfasserin aut Zeyu Xiong verfasserin aut Naina Kohli verfasserin aut Emily Larson verfasserin aut Mara L. G. Sullivan verfasserin aut Jonathan M. Franks verfasserin aut Donna B. Stolz verfasserin aut Ryota Ito verfasserin aut Kong Chen verfasserin aut Yohei Doi verfasserin aut Yohei Doi verfasserin aut Melanie J. Harriff verfasserin aut Melanie J. Harriff verfasserin aut Janet S. Lee verfasserin aut Janet S. Lee verfasserin aut Janet S. Lee verfasserin aut In Frontiers in Cellular and Infection Microbiology Frontiers Media S.A., 2016 13(2023) (DE-627)664968554 (DE-600)2619676-1 22352988 nnns volume:13 year:2023 https://doi.org/10.3389/fcimb.2023.1150658 kostenfrei https://doaj.org/article/d52c265d2f874b8fa7c45a112a78d396 kostenfrei https://www.frontiersin.org/articles/10.3389/fcimb.2023.1150658/full kostenfrei https://doaj.org/toc/2235-2988 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2023 |
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10.3389/fcimb.2023.1150658 doi (DE-627)DOAJ087486245 (DE-599)DOAJd52c265d2f874b8fa7c45a112a78d396 DE-627 ger DE-627 rakwb eng QR1-502 Rick van der Geest verfasserin aut Phagocytosis is a primary determinant of pulmonary clearance of clinical Klebsiella pneumoniae isolates 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionKlebsiella pneumoniae (Kp) is a common cause of hospital-acquired pneumonia. Although previous studies have suggested that evasion of phagocytic uptake is a virulence determinant of Kp, few studies have examined phagocytosis sensitivity in clinical Kp isolates.MethodsWe screened 19 clinical respiratory Kp isolates that were previously assessed for mucoviscosity for their sensitivity to macrophage phagocytic uptake, and evaluated phagocytosis as a functional correlate of in vivo Kp pathogenicity.ResultsThe respiratory Kp isolates displayed heterogeneity in the susceptibility to macrophage phagocytic uptake, with 14 out of 19 Kp isolates displaying relative phagocytosis-sensitivity compared to the reference Kp strain ATCC 43816, and 5 out of 19 Kp isolates displaying relative phagocytosis-resistance. Intratracheal infection with the non-mucoviscous phagocytosis-sensitive isolate S17 resulted in a significantly lower bacterial burden compared to infection with the mucoviscous phagocytosis-resistant isolate W42. In addition, infection with S17 was associated with a reduced inflammatory response, including reduced bronchoalveolar lavage fluid (BAL) polymorphonuclear (PMN) cell count, and reduced BAL TNF, IL-1β, and IL-12p40 levels. Importantly, host control of infection with the phagocytosis-sensitive S17 isolate was impaired in alveolar macrophage (AM)-depleted mice, whereas AM-depletion had no significant impact on host defense against infection with the phagocytosis-resistant W42 isolate.ConclusionAltogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical Kp isolates. respiratory infection host defense Klebsiella pneumoniae phagocytosis clinical isolates macrophages Microbiology Hongye Fan verfasserin aut Hernán F. Peñaloza verfasserin aut William G. Bain verfasserin aut William G. Bain verfasserin aut Zeyu Xiong verfasserin aut Naina Kohli verfasserin aut Emily Larson verfasserin aut Mara L. G. Sullivan verfasserin aut Jonathan M. Franks verfasserin aut Donna B. Stolz verfasserin aut Ryota Ito verfasserin aut Kong Chen verfasserin aut Yohei Doi verfasserin aut Yohei Doi verfasserin aut Melanie J. Harriff verfasserin aut Melanie J. Harriff verfasserin aut Janet S. Lee verfasserin aut Janet S. Lee verfasserin aut Janet S. Lee verfasserin aut In Frontiers in Cellular and Infection Microbiology Frontiers Media S.A., 2016 13(2023) (DE-627)664968554 (DE-600)2619676-1 22352988 nnns volume:13 year:2023 https://doi.org/10.3389/fcimb.2023.1150658 kostenfrei https://doaj.org/article/d52c265d2f874b8fa7c45a112a78d396 kostenfrei https://www.frontiersin.org/articles/10.3389/fcimb.2023.1150658/full kostenfrei https://doaj.org/toc/2235-2988 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2023 |
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10.3389/fcimb.2023.1150658 doi (DE-627)DOAJ087486245 (DE-599)DOAJd52c265d2f874b8fa7c45a112a78d396 DE-627 ger DE-627 rakwb eng QR1-502 Rick van der Geest verfasserin aut Phagocytosis is a primary determinant of pulmonary clearance of clinical Klebsiella pneumoniae isolates 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionKlebsiella pneumoniae (Kp) is a common cause of hospital-acquired pneumonia. Although previous studies have suggested that evasion of phagocytic uptake is a virulence determinant of Kp, few studies have examined phagocytosis sensitivity in clinical Kp isolates.MethodsWe screened 19 clinical respiratory Kp isolates that were previously assessed for mucoviscosity for their sensitivity to macrophage phagocytic uptake, and evaluated phagocytosis as a functional correlate of in vivo Kp pathogenicity.ResultsThe respiratory Kp isolates displayed heterogeneity in the susceptibility to macrophage phagocytic uptake, with 14 out of 19 Kp isolates displaying relative phagocytosis-sensitivity compared to the reference Kp strain ATCC 43816, and 5 out of 19 Kp isolates displaying relative phagocytosis-resistance. Intratracheal infection with the non-mucoviscous phagocytosis-sensitive isolate S17 resulted in a significantly lower bacterial burden compared to infection with the mucoviscous phagocytosis-resistant isolate W42. In addition, infection with S17 was associated with a reduced inflammatory response, including reduced bronchoalveolar lavage fluid (BAL) polymorphonuclear (PMN) cell count, and reduced BAL TNF, IL-1β, and IL-12p40 levels. Importantly, host control of infection with the phagocytosis-sensitive S17 isolate was impaired in alveolar macrophage (AM)-depleted mice, whereas AM-depletion had no significant impact on host defense against infection with the phagocytosis-resistant W42 isolate.ConclusionAltogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical Kp isolates. respiratory infection host defense Klebsiella pneumoniae phagocytosis clinical isolates macrophages Microbiology Hongye Fan verfasserin aut Hernán F. Peñaloza verfasserin aut William G. Bain verfasserin aut William G. Bain verfasserin aut Zeyu Xiong verfasserin aut Naina Kohli verfasserin aut Emily Larson verfasserin aut Mara L. G. Sullivan verfasserin aut Jonathan M. Franks verfasserin aut Donna B. Stolz verfasserin aut Ryota Ito verfasserin aut Kong Chen verfasserin aut Yohei Doi verfasserin aut Yohei Doi verfasserin aut Melanie J. Harriff verfasserin aut Melanie J. Harriff verfasserin aut Janet S. Lee verfasserin aut Janet S. Lee verfasserin aut Janet S. Lee verfasserin aut In Frontiers in Cellular and Infection Microbiology Frontiers Media S.A., 2016 13(2023) (DE-627)664968554 (DE-600)2619676-1 22352988 nnns volume:13 year:2023 https://doi.org/10.3389/fcimb.2023.1150658 kostenfrei https://doaj.org/article/d52c265d2f874b8fa7c45a112a78d396 kostenfrei https://www.frontiersin.org/articles/10.3389/fcimb.2023.1150658/full kostenfrei https://doaj.org/toc/2235-2988 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2023 |
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10.3389/fcimb.2023.1150658 doi (DE-627)DOAJ087486245 (DE-599)DOAJd52c265d2f874b8fa7c45a112a78d396 DE-627 ger DE-627 rakwb eng QR1-502 Rick van der Geest verfasserin aut Phagocytosis is a primary determinant of pulmonary clearance of clinical Klebsiella pneumoniae isolates 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionKlebsiella pneumoniae (Kp) is a common cause of hospital-acquired pneumonia. Although previous studies have suggested that evasion of phagocytic uptake is a virulence determinant of Kp, few studies have examined phagocytosis sensitivity in clinical Kp isolates.MethodsWe screened 19 clinical respiratory Kp isolates that were previously assessed for mucoviscosity for their sensitivity to macrophage phagocytic uptake, and evaluated phagocytosis as a functional correlate of in vivo Kp pathogenicity.ResultsThe respiratory Kp isolates displayed heterogeneity in the susceptibility to macrophage phagocytic uptake, with 14 out of 19 Kp isolates displaying relative phagocytosis-sensitivity compared to the reference Kp strain ATCC 43816, and 5 out of 19 Kp isolates displaying relative phagocytosis-resistance. Intratracheal infection with the non-mucoviscous phagocytosis-sensitive isolate S17 resulted in a significantly lower bacterial burden compared to infection with the mucoviscous phagocytosis-resistant isolate W42. In addition, infection with S17 was associated with a reduced inflammatory response, including reduced bronchoalveolar lavage fluid (BAL) polymorphonuclear (PMN) cell count, and reduced BAL TNF, IL-1β, and IL-12p40 levels. Importantly, host control of infection with the phagocytosis-sensitive S17 isolate was impaired in alveolar macrophage (AM)-depleted mice, whereas AM-depletion had no significant impact on host defense against infection with the phagocytosis-resistant W42 isolate.ConclusionAltogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical Kp isolates. respiratory infection host defense Klebsiella pneumoniae phagocytosis clinical isolates macrophages Microbiology Hongye Fan verfasserin aut Hernán F. Peñaloza verfasserin aut William G. Bain verfasserin aut William G. Bain verfasserin aut Zeyu Xiong verfasserin aut Naina Kohli verfasserin aut Emily Larson verfasserin aut Mara L. G. Sullivan verfasserin aut Jonathan M. Franks verfasserin aut Donna B. Stolz verfasserin aut Ryota Ito verfasserin aut Kong Chen verfasserin aut Yohei Doi verfasserin aut Yohei Doi verfasserin aut Melanie J. Harriff verfasserin aut Melanie J. Harriff verfasserin aut Janet S. Lee verfasserin aut Janet S. Lee verfasserin aut Janet S. Lee verfasserin aut In Frontiers in Cellular and Infection Microbiology Frontiers Media S.A., 2016 13(2023) (DE-627)664968554 (DE-600)2619676-1 22352988 nnns volume:13 year:2023 https://doi.org/10.3389/fcimb.2023.1150658 kostenfrei https://doaj.org/article/d52c265d2f874b8fa7c45a112a78d396 kostenfrei https://www.frontiersin.org/articles/10.3389/fcimb.2023.1150658/full kostenfrei https://doaj.org/toc/2235-2988 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2023 |
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10.3389/fcimb.2023.1150658 doi (DE-627)DOAJ087486245 (DE-599)DOAJd52c265d2f874b8fa7c45a112a78d396 DE-627 ger DE-627 rakwb eng QR1-502 Rick van der Geest verfasserin aut Phagocytosis is a primary determinant of pulmonary clearance of clinical Klebsiella pneumoniae isolates 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionKlebsiella pneumoniae (Kp) is a common cause of hospital-acquired pneumonia. Although previous studies have suggested that evasion of phagocytic uptake is a virulence determinant of Kp, few studies have examined phagocytosis sensitivity in clinical Kp isolates.MethodsWe screened 19 clinical respiratory Kp isolates that were previously assessed for mucoviscosity for their sensitivity to macrophage phagocytic uptake, and evaluated phagocytosis as a functional correlate of in vivo Kp pathogenicity.ResultsThe respiratory Kp isolates displayed heterogeneity in the susceptibility to macrophage phagocytic uptake, with 14 out of 19 Kp isolates displaying relative phagocytosis-sensitivity compared to the reference Kp strain ATCC 43816, and 5 out of 19 Kp isolates displaying relative phagocytosis-resistance. Intratracheal infection with the non-mucoviscous phagocytosis-sensitive isolate S17 resulted in a significantly lower bacterial burden compared to infection with the mucoviscous phagocytosis-resistant isolate W42. In addition, infection with S17 was associated with a reduced inflammatory response, including reduced bronchoalveolar lavage fluid (BAL) polymorphonuclear (PMN) cell count, and reduced BAL TNF, IL-1β, and IL-12p40 levels. Importantly, host control of infection with the phagocytosis-sensitive S17 isolate was impaired in alveolar macrophage (AM)-depleted mice, whereas AM-depletion had no significant impact on host defense against infection with the phagocytosis-resistant W42 isolate.ConclusionAltogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical Kp isolates. respiratory infection host defense Klebsiella pneumoniae phagocytosis clinical isolates macrophages Microbiology Hongye Fan verfasserin aut Hernán F. Peñaloza verfasserin aut William G. Bain verfasserin aut William G. Bain verfasserin aut Zeyu Xiong verfasserin aut Naina Kohli verfasserin aut Emily Larson verfasserin aut Mara L. G. Sullivan verfasserin aut Jonathan M. Franks verfasserin aut Donna B. Stolz verfasserin aut Ryota Ito verfasserin aut Kong Chen verfasserin aut Yohei Doi verfasserin aut Yohei Doi verfasserin aut Melanie J. Harriff verfasserin aut Melanie J. Harriff verfasserin aut Janet S. Lee verfasserin aut Janet S. Lee verfasserin aut Janet S. Lee verfasserin aut In Frontiers in Cellular and Infection Microbiology Frontiers Media S.A., 2016 13(2023) (DE-627)664968554 (DE-600)2619676-1 22352988 nnns volume:13 year:2023 https://doi.org/10.3389/fcimb.2023.1150658 kostenfrei https://doaj.org/article/d52c265d2f874b8fa7c45a112a78d396 kostenfrei https://www.frontiersin.org/articles/10.3389/fcimb.2023.1150658/full kostenfrei https://doaj.org/toc/2235-2988 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2023 |
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Rick van der Geest Hongye Fan Hernán F. Peñaloza William G. Bain Zeyu Xiong Naina Kohli Emily Larson Mara L. G. Sullivan Jonathan M. Franks Donna B. Stolz Ryota Ito Kong Chen Yohei Doi Melanie J. Harriff Janet S. Lee |
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phagocytosis is a primary determinant of pulmonary clearance of clinical klebsiella pneumoniae isolates |
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Phagocytosis is a primary determinant of pulmonary clearance of clinical Klebsiella pneumoniae isolates |
abstract |
IntroductionKlebsiella pneumoniae (Kp) is a common cause of hospital-acquired pneumonia. Although previous studies have suggested that evasion of phagocytic uptake is a virulence determinant of Kp, few studies have examined phagocytosis sensitivity in clinical Kp isolates.MethodsWe screened 19 clinical respiratory Kp isolates that were previously assessed for mucoviscosity for their sensitivity to macrophage phagocytic uptake, and evaluated phagocytosis as a functional correlate of in vivo Kp pathogenicity.ResultsThe respiratory Kp isolates displayed heterogeneity in the susceptibility to macrophage phagocytic uptake, with 14 out of 19 Kp isolates displaying relative phagocytosis-sensitivity compared to the reference Kp strain ATCC 43816, and 5 out of 19 Kp isolates displaying relative phagocytosis-resistance. Intratracheal infection with the non-mucoviscous phagocytosis-sensitive isolate S17 resulted in a significantly lower bacterial burden compared to infection with the mucoviscous phagocytosis-resistant isolate W42. In addition, infection with S17 was associated with a reduced inflammatory response, including reduced bronchoalveolar lavage fluid (BAL) polymorphonuclear (PMN) cell count, and reduced BAL TNF, IL-1β, and IL-12p40 levels. Importantly, host control of infection with the phagocytosis-sensitive S17 isolate was impaired in alveolar macrophage (AM)-depleted mice, whereas AM-depletion had no significant impact on host defense against infection with the phagocytosis-resistant W42 isolate.ConclusionAltogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical Kp isolates. |
abstractGer |
IntroductionKlebsiella pneumoniae (Kp) is a common cause of hospital-acquired pneumonia. Although previous studies have suggested that evasion of phagocytic uptake is a virulence determinant of Kp, few studies have examined phagocytosis sensitivity in clinical Kp isolates.MethodsWe screened 19 clinical respiratory Kp isolates that were previously assessed for mucoviscosity for their sensitivity to macrophage phagocytic uptake, and evaluated phagocytosis as a functional correlate of in vivo Kp pathogenicity.ResultsThe respiratory Kp isolates displayed heterogeneity in the susceptibility to macrophage phagocytic uptake, with 14 out of 19 Kp isolates displaying relative phagocytosis-sensitivity compared to the reference Kp strain ATCC 43816, and 5 out of 19 Kp isolates displaying relative phagocytosis-resistance. Intratracheal infection with the non-mucoviscous phagocytosis-sensitive isolate S17 resulted in a significantly lower bacterial burden compared to infection with the mucoviscous phagocytosis-resistant isolate W42. In addition, infection with S17 was associated with a reduced inflammatory response, including reduced bronchoalveolar lavage fluid (BAL) polymorphonuclear (PMN) cell count, and reduced BAL TNF, IL-1β, and IL-12p40 levels. Importantly, host control of infection with the phagocytosis-sensitive S17 isolate was impaired in alveolar macrophage (AM)-depleted mice, whereas AM-depletion had no significant impact on host defense against infection with the phagocytosis-resistant W42 isolate.ConclusionAltogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical Kp isolates. |
abstract_unstemmed |
IntroductionKlebsiella pneumoniae (Kp) is a common cause of hospital-acquired pneumonia. Although previous studies have suggested that evasion of phagocytic uptake is a virulence determinant of Kp, few studies have examined phagocytosis sensitivity in clinical Kp isolates.MethodsWe screened 19 clinical respiratory Kp isolates that were previously assessed for mucoviscosity for their sensitivity to macrophage phagocytic uptake, and evaluated phagocytosis as a functional correlate of in vivo Kp pathogenicity.ResultsThe respiratory Kp isolates displayed heterogeneity in the susceptibility to macrophage phagocytic uptake, with 14 out of 19 Kp isolates displaying relative phagocytosis-sensitivity compared to the reference Kp strain ATCC 43816, and 5 out of 19 Kp isolates displaying relative phagocytosis-resistance. Intratracheal infection with the non-mucoviscous phagocytosis-sensitive isolate S17 resulted in a significantly lower bacterial burden compared to infection with the mucoviscous phagocytosis-resistant isolate W42. In addition, infection with S17 was associated with a reduced inflammatory response, including reduced bronchoalveolar lavage fluid (BAL) polymorphonuclear (PMN) cell count, and reduced BAL TNF, IL-1β, and IL-12p40 levels. Importantly, host control of infection with the phagocytosis-sensitive S17 isolate was impaired in alveolar macrophage (AM)-depleted mice, whereas AM-depletion had no significant impact on host defense against infection with the phagocytosis-resistant W42 isolate.ConclusionAltogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical Kp isolates. |
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Phagocytosis is a primary determinant of pulmonary clearance of clinical Klebsiella pneumoniae isolates |
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https://doi.org/10.3389/fcimb.2023.1150658 https://doaj.org/article/d52c265d2f874b8fa7c45a112a78d396 https://www.frontiersin.org/articles/10.3389/fcimb.2023.1150658/full https://doaj.org/toc/2235-2988 |
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Hongye Fan Hernán F. Peñaloza William G. Bain Zeyu Xiong Naina Kohli Emily Larson Mara L. G. Sullivan Jonathan M. Franks Donna B. Stolz Ryota Ito Kong Chen Yohei Doi Melanie J. Harriff Janet S. Lee |
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