Decreased inflammatory response in Toll-like receptor 2 knockout mice is associated with exacerbated Pneumocystis pneumonia

Shao Hung Wang; Chen Zhang; Mark E. Lasbury; Chung Ping Liao; Pamela J. Durant; Dennis Tschang; Chao Hung Lee

doi:10.1016/j.micinf.2007.12.014

Decreased inflammatory response in Toll-like receptor 2 knockout mice is associated with exacerbated Pneumocystis pneumonia

Shao Hung Wang, Chen Zhang, Mark E. Lasbury, Chung Ping Liao, Pamela J. Durant, Dennis Tschang, Chao Hung Lee

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Pneumocystis pneumonia (PcP) is marked by substantial inflammatory damage to the lung. We have found that Toll-like receptor 2 (TLR2) mediates macrophage inflammatory responses to Pneumocystis and hypothesized that TLR2 deficiency would lead to less severe inflammation and milder lung injury during PcP. Histopathology examination showed that TLR2-/- mice with PcP indeed exhibited milder pulmonary inflammation. TLR2-/- mouse lungs contained less TNF-α and displayed lower levels of NF-κB activation during PcP. However, TLR2-/- mice with PcP displayed increased severity in symptoms and organism burden. The increased organism burden is likely due to defects in protective mechanisms in TLR2-/- mice. mRNA levels of the inducible nitric oxide synthase and NADPH oxidase p47phox, as well as nitric oxide levels in the lungs, were decreased in TLR2-/- PcP mice. Taken together, this study shows that TLR2-mediated inflammatory responses contribute to a certain degree to the clearance of Pneumocystis organism in mice.

Original language	English (US)
Pages (from-to)	334-341
Number of pages	8
Journal	Microbes and Infection
Volume	10
Issue number	4
DOIs	https://doi.org/10.1016/j.micinf.2007.12.014
State	Published - Apr 2008

Keywords

Inflammation
Pneumocystis
Toll-like receptor 2

ASJC Scopus subject areas

Microbiology
Immunology
Infectious Diseases

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10.1016/j.micinf.2007.12.014

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title = "Decreased inflammatory response in Toll-like receptor 2 knockout mice is associated with exacerbated Pneumocystis pneumonia",

abstract = "Pneumocystis pneumonia (PcP) is marked by substantial inflammatory damage to the lung. We have found that Toll-like receptor 2 (TLR2) mediates macrophage inflammatory responses to Pneumocystis and hypothesized that TLR2 deficiency would lead to less severe inflammation and milder lung injury during PcP. Histopathology examination showed that TLR2-/- mice with PcP indeed exhibited milder pulmonary inflammation. TLR2-/- mouse lungs contained less TNF-α and displayed lower levels of NF-κB activation during PcP. However, TLR2-/- mice with PcP displayed increased severity in symptoms and organism burden. The increased organism burden is likely due to defects in protective mechanisms in TLR2-/- mice. mRNA levels of the inducible nitric oxide synthase and NADPH oxidase p47phox, as well as nitric oxide levels in the lungs, were decreased in TLR2-/- PcP mice. Taken together, this study shows that TLR2-mediated inflammatory responses contribute to a certain degree to the clearance of Pneumocystis organism in mice.",

keywords = "Inflammation, Pneumocystis, Toll-like receptor 2",

author = "Wang, {Shao Hung} and Chen Zhang and Lasbury, {Mark E.} and Liao, {Chung Ping} and Durant, {Pamela J.} and Dennis Tschang and Lee, {Chao Hung}",

note = "Funding Information: The study was supported by grants from the National Institutes of Health (RO1 HL65170 and RO1 AI062259).",

year = "2008",

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doi = "10.1016/j.micinf.2007.12.014",

language = "English (US)",

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AU - Wang, Shao Hung

AU - Zhang, Chen

AU - Lasbury, Mark E.

AU - Liao, Chung Ping

AU - Durant, Pamela J.

AU - Tschang, Dennis

AU - Lee, Chao Hung

N1 - Funding Information: The study was supported by grants from the National Institutes of Health (RO1 HL65170 and RO1 AI062259).

PY - 2008/4

Y1 - 2008/4

N2 - Pneumocystis pneumonia (PcP) is marked by substantial inflammatory damage to the lung. We have found that Toll-like receptor 2 (TLR2) mediates macrophage inflammatory responses to Pneumocystis and hypothesized that TLR2 deficiency would lead to less severe inflammation and milder lung injury during PcP. Histopathology examination showed that TLR2-/- mice with PcP indeed exhibited milder pulmonary inflammation. TLR2-/- mouse lungs contained less TNF-α and displayed lower levels of NF-κB activation during PcP. However, TLR2-/- mice with PcP displayed increased severity in symptoms and organism burden. The increased organism burden is likely due to defects in protective mechanisms in TLR2-/- mice. mRNA levels of the inducible nitric oxide synthase and NADPH oxidase p47phox, as well as nitric oxide levels in the lungs, were decreased in TLR2-/- PcP mice. Taken together, this study shows that TLR2-mediated inflammatory responses contribute to a certain degree to the clearance of Pneumocystis organism in mice.

AB - Pneumocystis pneumonia (PcP) is marked by substantial inflammatory damage to the lung. We have found that Toll-like receptor 2 (TLR2) mediates macrophage inflammatory responses to Pneumocystis and hypothesized that TLR2 deficiency would lead to less severe inflammation and milder lung injury during PcP. Histopathology examination showed that TLR2-/- mice with PcP indeed exhibited milder pulmonary inflammation. TLR2-/- mouse lungs contained less TNF-α and displayed lower levels of NF-κB activation during PcP. However, TLR2-/- mice with PcP displayed increased severity in symptoms and organism burden. The increased organism burden is likely due to defects in protective mechanisms in TLR2-/- mice. mRNA levels of the inducible nitric oxide synthase and NADPH oxidase p47phox, as well as nitric oxide levels in the lungs, were decreased in TLR2-/- PcP mice. Taken together, this study shows that TLR2-mediated inflammatory responses contribute to a certain degree to the clearance of Pneumocystis organism in mice.

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KW - Toll-like receptor 2

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Decreased inflammatory response in Toll-like receptor 2 knockout mice is associated with exacerbated Pneumocystis pneumonia

Abstract

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