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Home / Equine Research Bank / Infect Immun / Cytokine modulation alters pulmonary clearance of Rhodococcu...
Infection and immunity1995; 63(8); 3037-3041; doi: 10.1128/iai.63.8.3037-3041.1995

Cytokine modulation alters pulmonary clearance of Rhodococcus equi and development of granulomatous pneumonia.

Abstract: Rhodococcus equi, a facultative intracellular bacterium, causes chronic, often fatal granulomatous pneumonia in young horses and in humans with AIDS. The inability of host alveolar macrophages to kill intracellular R. equi results in the development of granulomas and progressive loss of pulmonary parenchyma. Clearance of the organism from the lung requires functional CD4+ T cells. The purpose of this study was to identify the cytokine effector mechanisms that mediate clearance of R. equi from the lung. Mice were treated with monoclonal antibodies (MAbs) to either gamma interferon (IFN-gamma) or interleukin-4 (IL-4) to determine the role of endogenous production of these cytokines in pulmonary clearance of R. equi. Mice treated with an anti-IL-4 or isotype control MAb cleared R. equi by 21 days postinfection and expressed increased levels of IFN-gamma mRNA, as detected by transcriptional analysis of bronchial lymph node CD4+ T cells. In contrast, mice treated with the anti-IFN-gamma MAb failed to express detectable IFN-gamma mRNA, expressed increased levels of IL-4 mRNA, failed to clear pulmonary infection, and developed pulmonary granulomas with large numbers of eosinophils. The enhancement of IL-4 mRNA expression and a predominance of eosinophils in pulmonary lesions of anti-IFN-gamma-treated mice suggest that a nonprotective Th2 response in involved in disease pathogenesis. The association of increased bronchial lymph node CD4+ T-cell IFN-gamma mRNA expression with pulmonary clearance of R. equi suggests that a Th1 response is protective.
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Publication Date: 1995-08-01 PubMed ID: 7622227PubMed Central: PMC173413DOI: 10.1128/iai.63.8.3037-3041.1995Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article explores how modifying cytokine activity can impact the clearance of the bacterium Rhodococcus equi from the lungs, and consequently the development of a type of pneumonia known as granulomatous pneumonia in mice.

Objective and Purpose of the Study

  • This study investigates how cytokine effector mechanisms affect the clearance of Rhodococcus equi, a bacterium that causes chronic and often fatal granulomatous pneumonia, from the lungs.
  • The researchers sought to determine the roles of gamma interferon (IFN-gamma) and interleukin-4 (IL-4)—two types of cytokines—in the clearance of this bacterium.

Methodology

  • Mice were used as subjects for the study. They were treated with monoclonal antibodies (MAbs) to IFN-gamma or IL-4, to simulate different conditions of cytokine production.
  • Conditions with different levels of IFN-gamma or IL-4 were analyzed to understand their impact on the clearance of Rhodococcus equi from the lungs.
  • The researchers monitored and measured mRNA expression levels of these cytokines in bronchial lymph node CD4+ T cells through transcriptional analysis.

Observations and Findings

  • Mice treated with anti-IL-4 or isotype control monoclonal antibody cleared Rhodococcus equi from their lungs by the 21st day post infection. These mice expressed increased levels of IFN-gamma mRNA, suggesting a role of this cytokine in successful bacterial clearance.
  • However, mice treated with an anti-IFN-gamma monoclonal antibody expressed increased levels of IL-4 mRNA. These mice were unable to clear the infection and developed pulmonary granulomas with a large number of eosinophils. This suggests that an increase in IL-4 leads to a non-protective response and contributes to disease progression.
  • The experiment therefore suggested that a protective Th1 response, associated with increased IFN-gamma mRNA expression, aids in the clearance of R. equi, while a non-protective Th2 response, associated with enhanced IL-4 mRNA expression, is implicated in disease pathogenesis.

Cite This Article

APA
Kanaly ST, Hines SA, Palmer GH. (1995). Cytokine modulation alters pulmonary clearance of Rhodococcus equi and development of granulomatous pneumonia. Infect Immun, 63(8), 3037-3041. https://doi.org/10.1128/iai.63.8.3037-3041.1995

Publication

Infection and immunity
ISSN: 0019-9567
NlmUniqueID: 0246127
Country: United States
Language: English
Volume: 63
Issue: 8
Pages: 3037-3041

Researcher Affiliations

Kanaly, S T
  • Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164-7040, USA.
Hines, S A
    Palmer, G H

      MeSH Terms

      • Actinomycetales Infections / immunology
      • Animals
      • Female
      • Gene Expression
      • Interferon-gamma / physiology
      • Interleukin-4 / physiology
      • Lung / immunology
      • Lung / pathology
      • Mice
      • Mice, Inbred BALB C
      • Pneumonia / immunology
      • Pneumonia / microbiology
      • RNA, Messenger / genetics
      • Rhodococcus equi / immunology
      • Th1 Cells / immunology
      • Th2 Cells / immunology

      Grant Funding

      • 1 K11 AI 01233-01 / NIAID NIH HHS
      • 5 T32 AI 07025-14 / NIAID NIH HHS

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      Citations

      This article has been cited 24 times.
      1. Xu Z, Hao X, Li M, Luo H. Rhodococcus equi-Derived Extracellular Vesicles Promoting Inflammatory Response in Macrophage through TLR2-NF-κB/MAPK Pathways.. Int J Mol Sci 2022 Aug 28;23(17).
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