Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia

K. Tateda, T. A. Moore, J. C. Deng, M. W. Newstead, X. Zeng, Akihiro Matsukawa, M. S. Swanson, K. Yamaguchi, T. J. Standiford

Research output: Contribution to journalArticle

171 Citations (Scopus)

Abstract

The contribution of neutrophils to lethal sensitivity and cytokine balance governing T1 and T2 host responses was assessed in a murine model of Legionella pneumophila pneumonia. Neutrophil depletion by administration of granulocyte-specific mAb RB6-8C5 at 1 day before infection rendered mice ∼100-fold more susceptible to lethal pneumonia induced by L. pneumophila. However, this treatment did not alter early bacterial clearance, despite a substantial decrease in neutrophil influx at this time point. Cytokine profiles in the lungs of control mice demonstrated strong T1 responses, characterized by an increase of IFN-γ and IL-12. In contrast, neutrophil-depleted mice exhibited significantly lower levels of IFN-γ and IL-12, and elevation of T2 cytokines, IL-4 and IL-10. Immunohistochemistry of bronchoalveolar lavage cells demonstrated the presence of IL-12 in neutrophils, but not alveolar macrophages. Moreover, IL-12 was detected in lavage cell lysates by ELISA, which was paralleled to neutrophil number. However, intratracheal administration of recombinant murine IL-12 did not restore resistance, whereas reconstitution of IFN-γ drastically improved bacterial clearance and survival in neutrophil-depleted mice. Taken together, these data demonstrated that neutrophils play crucial roles in primary L. pneumophila infection, not via direct killing but more immunomodulatory effects. Our results suggest that the early recruitment of neutrophils may contribute to T1 polarization in a murine model of L. pneumophila pneumonia.

Original languageEnglish
Pages (from-to)3355-3361
Number of pages7
JournalJournal of Immunology
Volume166
Issue number5
Publication statusPublished - Mar 1 2001
Externally publishedYes

Fingerprint

Legionella pneumophila
Neutrophil Infiltration
Pneumonia
Neutrophils
Interleukin-12
Cytokines
Legionnaires' Disease
Therapeutic Irrigation
Alveolar Macrophages
Bronchoalveolar Lavage
Granulocytes
Interleukin-4
Interleukin-10
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Lung
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Tateda, K., Moore, T. A., Deng, J. C., Newstead, M. W., Zeng, X., Matsukawa, A., ... Standiford, T. J. (2001). Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia. Journal of Immunology, 166(5), 3355-3361.

Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia. / Tateda, K.; Moore, T. A.; Deng, J. C.; Newstead, M. W.; Zeng, X.; Matsukawa, Akihiro; Swanson, M. S.; Yamaguchi, K.; Standiford, T. J.

In: Journal of Immunology, Vol. 166, No. 5, 01.03.2001, p. 3355-3361.

Research output: Contribution to journalArticle

Tateda, K, Moore, TA, Deng, JC, Newstead, MW, Zeng, X, Matsukawa, A, Swanson, MS, Yamaguchi, K & Standiford, TJ 2001, 'Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia', Journal of Immunology, vol. 166, no. 5, pp. 3355-3361.
Tateda, K. ; Moore, T. A. ; Deng, J. C. ; Newstead, M. W. ; Zeng, X. ; Matsukawa, Akihiro ; Swanson, M. S. ; Yamaguchi, K. ; Standiford, T. J. / Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia. In: Journal of Immunology. 2001 ; Vol. 166, No. 5. pp. 3355-3361.
@article{0b64449fd0c641348b92e423e8de7e39,
title = "Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia",
abstract = "The contribution of neutrophils to lethal sensitivity and cytokine balance governing T1 and T2 host responses was assessed in a murine model of Legionella pneumophila pneumonia. Neutrophil depletion by administration of granulocyte-specific mAb RB6-8C5 at 1 day before infection rendered mice ∼100-fold more susceptible to lethal pneumonia induced by L. pneumophila. However, this treatment did not alter early bacterial clearance, despite a substantial decrease in neutrophil influx at this time point. Cytokine profiles in the lungs of control mice demonstrated strong T1 responses, characterized by an increase of IFN-γ and IL-12. In contrast, neutrophil-depleted mice exhibited significantly lower levels of IFN-γ and IL-12, and elevation of T2 cytokines, IL-4 and IL-10. Immunohistochemistry of bronchoalveolar lavage cells demonstrated the presence of IL-12 in neutrophils, but not alveolar macrophages. Moreover, IL-12 was detected in lavage cell lysates by ELISA, which was paralleled to neutrophil number. However, intratracheal administration of recombinant murine IL-12 did not restore resistance, whereas reconstitution of IFN-γ drastically improved bacterial clearance and survival in neutrophil-depleted mice. Taken together, these data demonstrated that neutrophils play crucial roles in primary L. pneumophila infection, not via direct killing but more immunomodulatory effects. Our results suggest that the early recruitment of neutrophils may contribute to T1 polarization in a murine model of L. pneumophila pneumonia.",
author = "K. Tateda and Moore, {T. A.} and Deng, {J. C.} and Newstead, {M. W.} and X. Zeng and Akihiro Matsukawa and Swanson, {M. S.} and K. Yamaguchi and Standiford, {T. J.}",
year = "2001",
month = "3",
day = "1",
language = "English",
volume = "166",
pages = "3355--3361",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

TY - JOUR

T1 - Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia

AU - Tateda, K.

AU - Moore, T. A.

AU - Deng, J. C.

AU - Newstead, M. W.

AU - Zeng, X.

AU - Matsukawa, Akihiro

AU - Swanson, M. S.

AU - Yamaguchi, K.

AU - Standiford, T. J.

PY - 2001/3/1

Y1 - 2001/3/1

N2 - The contribution of neutrophils to lethal sensitivity and cytokine balance governing T1 and T2 host responses was assessed in a murine model of Legionella pneumophila pneumonia. Neutrophil depletion by administration of granulocyte-specific mAb RB6-8C5 at 1 day before infection rendered mice ∼100-fold more susceptible to lethal pneumonia induced by L. pneumophila. However, this treatment did not alter early bacterial clearance, despite a substantial decrease in neutrophil influx at this time point. Cytokine profiles in the lungs of control mice demonstrated strong T1 responses, characterized by an increase of IFN-γ and IL-12. In contrast, neutrophil-depleted mice exhibited significantly lower levels of IFN-γ and IL-12, and elevation of T2 cytokines, IL-4 and IL-10. Immunohistochemistry of bronchoalveolar lavage cells demonstrated the presence of IL-12 in neutrophils, but not alveolar macrophages. Moreover, IL-12 was detected in lavage cell lysates by ELISA, which was paralleled to neutrophil number. However, intratracheal administration of recombinant murine IL-12 did not restore resistance, whereas reconstitution of IFN-γ drastically improved bacterial clearance and survival in neutrophil-depleted mice. Taken together, these data demonstrated that neutrophils play crucial roles in primary L. pneumophila infection, not via direct killing but more immunomodulatory effects. Our results suggest that the early recruitment of neutrophils may contribute to T1 polarization in a murine model of L. pneumophila pneumonia.

AB - The contribution of neutrophils to lethal sensitivity and cytokine balance governing T1 and T2 host responses was assessed in a murine model of Legionella pneumophila pneumonia. Neutrophil depletion by administration of granulocyte-specific mAb RB6-8C5 at 1 day before infection rendered mice ∼100-fold more susceptible to lethal pneumonia induced by L. pneumophila. However, this treatment did not alter early bacterial clearance, despite a substantial decrease in neutrophil influx at this time point. Cytokine profiles in the lungs of control mice demonstrated strong T1 responses, characterized by an increase of IFN-γ and IL-12. In contrast, neutrophil-depleted mice exhibited significantly lower levels of IFN-γ and IL-12, and elevation of T2 cytokines, IL-4 and IL-10. Immunohistochemistry of bronchoalveolar lavage cells demonstrated the presence of IL-12 in neutrophils, but not alveolar macrophages. Moreover, IL-12 was detected in lavage cell lysates by ELISA, which was paralleled to neutrophil number. However, intratracheal administration of recombinant murine IL-12 did not restore resistance, whereas reconstitution of IFN-γ drastically improved bacterial clearance and survival in neutrophil-depleted mice. Taken together, these data demonstrated that neutrophils play crucial roles in primary L. pneumophila infection, not via direct killing but more immunomodulatory effects. Our results suggest that the early recruitment of neutrophils may contribute to T1 polarization in a murine model of L. pneumophila pneumonia.

UR - http://www.scopus.com/inward/record.url?scp=0035284832&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035284832&partnerID=8YFLogxK

M3 - Article

C2 - 11207291

AN - SCOPUS:0035284832

VL - 166

SP - 3355

EP - 3361

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

ER -