Toll-like receptor 2 mediates alveolar macrophage response to Pneumocystis murina

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

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

The innate immune response to Pneumocystis infection is not well understood. In this study, normal C57BL/6 mouse alveolar macrophages were found to respond to Pneumocystis murina organisms through Toll-like receptor 2 (TLR2), leading to the nuclear translocation of NF-κB and the production of proinflammatory cytokine tumor necrosis factor alpha (TNF-α) and chemokine macrophage inflammatory protein 2 (MIP-2). P. murina stimulation of normal alveolar macrophages from C57BL/6 mice resulted in increased TLR2 transcription but not increased TLR4 transcription. In gain-of-function studies with HEK293 cells expressing TLR2 or TLR4, only TLR2 was found to stimulate an NF-κB response to P. murina. TNF-α and MIP-2 production in response to P. murina by moose alveolar macrophages was inhibited by a monoclonal antibody that specifically blocked the ligand-binding ability of TLR2. Alveolar macrophages from TLR2 knockout (TLR2-/-) mice showed little increase in TNF-α and MIP-2 mRNA levels upon P. murina stimulation. An in vivo study showed that TLR2-/- mice challenged with P. murina had reduced cytokine responses. These results indicate that TLR2 plays a major role in the innate immune response to P. murina.

Original languageEnglish (US)
Pages (from-to)1857-1864
Number of pages8
JournalInfection and Immunity
Volume74
Issue number3
DOIs
StatePublished - Mar 1 2006

Fingerprint

Pneumocystis
Murinae
Toll-Like Receptor 2
Alveolar Macrophages
Chemokine CXCL2
Tumor Necrosis Factor-alpha
Inbred C57BL Mouse
Innate Immunity
Pneumocystis Infections
Cytokines
CXC Chemokines
HEK293 Cells
Knockout Mice
Monoclonal Antibodies
Ligands
Messenger RNA

ASJC Scopus subject areas

  • Immunology

Cite this

Zhang, C., Wang, S. H., Lasbury, M. E., Tschang, D., Liao, C. P., Durant, P. J., & Lee, C. H. (2006). Toll-like receptor 2 mediates alveolar macrophage response to Pneumocystis murina. Infection and Immunity, 74(3), 1857-1864. https://doi.org/10.1128/IAI.74.3.1857-1864.2006

Toll-like receptor 2 mediates alveolar macrophage response to Pneumocystis murina. / Zhang, Chen; Wang, Shao Hung; Lasbury, Mark E.; Tschang, Dennis; Liao, Chung Ping; Durant, Pamela J.; Lee, Chao Hung.

In: Infection and Immunity, Vol. 74, No. 3, 01.03.2006, p. 1857-1864.

Research output: Contribution to journalArticle

Zhang, C, Wang, SH, Lasbury, ME, Tschang, D, Liao, CP, Durant, PJ & Lee, CH 2006, 'Toll-like receptor 2 mediates alveolar macrophage response to Pneumocystis murina', Infection and Immunity, vol. 74, no. 3, pp. 1857-1864. https://doi.org/10.1128/IAI.74.3.1857-1864.2006
Zhang, Chen ; Wang, Shao Hung ; Lasbury, Mark E. ; Tschang, Dennis ; Liao, Chung Ping ; Durant, Pamela J. ; Lee, Chao Hung. / Toll-like receptor 2 mediates alveolar macrophage response to Pneumocystis murina. In: Infection and Immunity. 2006 ; Vol. 74, No. 3. pp. 1857-1864.
@article{c7840d3ad05e4721874ff6dc39cd17c4,
title = "Toll-like receptor 2 mediates alveolar macrophage response to Pneumocystis murina",
abstract = "The innate immune response to Pneumocystis infection is not well understood. In this study, normal C57BL/6 mouse alveolar macrophages were found to respond to Pneumocystis murina organisms through Toll-like receptor 2 (TLR2), leading to the nuclear translocation of NF-κB and the production of proinflammatory cytokine tumor necrosis factor alpha (TNF-α) and chemokine macrophage inflammatory protein 2 (MIP-2). P. murina stimulation of normal alveolar macrophages from C57BL/6 mice resulted in increased TLR2 transcription but not increased TLR4 transcription. In gain-of-function studies with HEK293 cells expressing TLR2 or TLR4, only TLR2 was found to stimulate an NF-κB response to P. murina. TNF-α and MIP-2 production in response to P. murina by moose alveolar macrophages was inhibited by a monoclonal antibody that specifically blocked the ligand-binding ability of TLR2. Alveolar macrophages from TLR2 knockout (TLR2-/-) mice showed little increase in TNF-α and MIP-2 mRNA levels upon P. murina stimulation. An in vivo study showed that TLR2-/- mice challenged with P. murina had reduced cytokine responses. These results indicate that TLR2 plays a major role in the innate immune response to P. murina.",
author = "Chen Zhang and Wang, {Shao Hung} and Lasbury, {Mark E.} and Dennis Tschang and Liao, {Chung Ping} and Durant, {Pamela J.} and Lee, {Chao Hung}",
year = "2006",
month = "3",
day = "1",
doi = "10.1128/IAI.74.3.1857-1864.2006",
language = "English (US)",
volume = "74",
pages = "1857--1864",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "3",

}

TY - JOUR

T1 - Toll-like receptor 2 mediates alveolar macrophage response to Pneumocystis murina

AU - Zhang, Chen

AU - Wang, Shao Hung

AU - Lasbury, Mark E.

AU - Tschang, Dennis

AU - Liao, Chung Ping

AU - Durant, Pamela J.

AU - Lee, Chao Hung

PY - 2006/3/1

Y1 - 2006/3/1

N2 - The innate immune response to Pneumocystis infection is not well understood. In this study, normal C57BL/6 mouse alveolar macrophages were found to respond to Pneumocystis murina organisms through Toll-like receptor 2 (TLR2), leading to the nuclear translocation of NF-κB and the production of proinflammatory cytokine tumor necrosis factor alpha (TNF-α) and chemokine macrophage inflammatory protein 2 (MIP-2). P. murina stimulation of normal alveolar macrophages from C57BL/6 mice resulted in increased TLR2 transcription but not increased TLR4 transcription. In gain-of-function studies with HEK293 cells expressing TLR2 or TLR4, only TLR2 was found to stimulate an NF-κB response to P. murina. TNF-α and MIP-2 production in response to P. murina by moose alveolar macrophages was inhibited by a monoclonal antibody that specifically blocked the ligand-binding ability of TLR2. Alveolar macrophages from TLR2 knockout (TLR2-/-) mice showed little increase in TNF-α and MIP-2 mRNA levels upon P. murina stimulation. An in vivo study showed that TLR2-/- mice challenged with P. murina had reduced cytokine responses. These results indicate that TLR2 plays a major role in the innate immune response to P. murina.

AB - The innate immune response to Pneumocystis infection is not well understood. In this study, normal C57BL/6 mouse alveolar macrophages were found to respond to Pneumocystis murina organisms through Toll-like receptor 2 (TLR2), leading to the nuclear translocation of NF-κB and the production of proinflammatory cytokine tumor necrosis factor alpha (TNF-α) and chemokine macrophage inflammatory protein 2 (MIP-2). P. murina stimulation of normal alveolar macrophages from C57BL/6 mice resulted in increased TLR2 transcription but not increased TLR4 transcription. In gain-of-function studies with HEK293 cells expressing TLR2 or TLR4, only TLR2 was found to stimulate an NF-κB response to P. murina. TNF-α and MIP-2 production in response to P. murina by moose alveolar macrophages was inhibited by a monoclonal antibody that specifically blocked the ligand-binding ability of TLR2. Alveolar macrophages from TLR2 knockout (TLR2-/-) mice showed little increase in TNF-α and MIP-2 mRNA levels upon P. murina stimulation. An in vivo study showed that TLR2-/- mice challenged with P. murina had reduced cytokine responses. These results indicate that TLR2 plays a major role in the innate immune response to P. murina.

UR - http://www.scopus.com/inward/record.url?scp=33644778608&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644778608&partnerID=8YFLogxK

U2 - 10.1128/IAI.74.3.1857-1864.2006

DO - 10.1128/IAI.74.3.1857-1864.2006

M3 - Article

VL - 74

SP - 1857

EP - 1864

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 3

ER -