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Evolution of the primary immune response to Histoplasma capsulatum in murine lung
1Department of Medicine, University of Cincinnati College of Medicine, Ohio 45267-0560, USA.
Abstract:
Histoplasma capsulatum induces a cell-mediated immune response in the lungs and lymphoid organs of mammals. In this study, we analyzed the progression of the cytokine and inflammatory reactions in the lungs of mice infected intranasally with H. capsulatum. We measured cytokine mRNA levels and determined the inflammatory cell populations during the active phase of infection (<3 weeks). Transcription of genes encoding interleukin-2 (IL-2), IL-4, and IL-12 and gamma interferon (IFN-gamma) was detectable as early as day 3 of infection, whereas a signal for IL-10 was never observed. Competitive PCR analysis demonstrated that enhanced expression of IL-12 mRNA was observed by day 3 and that expression of mRNA for IL-2 and IFN-gamma progressively increased from day 5 to day 10. All levels declined by day 14. Analysis of the inflammatory response revealed an initial elevation in myeloid cells (Mac-1+) and natural killer (NK) cells followed by a rise in T cells, predominantly CD4+ cells. Since IFN-gamma is a key factor in host defense, we performed cytoplasmic staining to determine the cell populations that produced this cytokine. The hierarchy of synthesis was CD4+ > CD8+ > NK cells. Thus, H. capsulatum provokes an orderly modulation of the inflammatory and cytokine responses in murine lungs.
Insights
Histoplasma capsulatum infection triggers specific immune responses in mouse lungs, characterized by early cytokine production and a sequential influx of immune cells. This study details the inflammatory progression and key cytokine involvement during the acute infection phase.
Area of Science:
- Immunology
- Microbiology
- Pulmonary Medicine
Background:
- Histoplasma capsulatum is a fungal pathogen that elicits a cell-mediated immune response.
- Understanding the dynamics of pulmonary inflammation and cytokine profiles is crucial for managing histoplasmosis.
Purpose of the Study:
- To analyze the progression of cytokine and inflammatory reactions in mouse lungs following intranasal H. capsulatum infection.
- To identify key immune cells and cytokines involved during the acute phase of infection.
Main Methods:
- Mice were infected intranasally with H. capsulatum.
- Cytokine mRNA levels were measured using competitive PCR.
- Inflammatory cell populations were determined by flow cytometry.
- Intracellular cytokine staining was performed to identify IFN-gamma producing cells.
Main Results:
- Transcription of IL-2, IL-4, IL-12, and IFN-gamma was detected by day 3; IL-10 was not observed.
- IL-12 mRNA expression increased by day 3, followed by progressive increases in IL-2 and IFN-gamma from day 5 to day 10.
- Inflammatory response included myeloid cells, NK cells, and predominantly CD4+ T cells.
- CD4+ T cells were the primary producers of IFN-gamma, followed by CD8+ T cells and NK cells.
Conclusions:
- H. capsulatum infection induces an ordered inflammatory and cytokine response in murine lungs.
- The study highlights the sequential activation of immune cells and the critical role of IFN-gamma in host defense against H. capsulatum.