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In vivo Imaging of Transgenic Leishmania Parasites in a Live Host
Published on: July 28, 2010
Nitric oxide and cellular immunity in experimental cutaneous leishmaniasis
N L Díaz1, M Fernández, E Figueira
1Laboratorio de Biología Molecular, Instituto de Biomedicina, Universidad Central de Venezuela, Caracas, Venezuela.
Abstract:
We examined the local and systemic production of nitric oxide (NO) and the pattern of cytokine during the course of Leishmania mexicana infection in susceptible BALB/c and resistant C57BL/6 mice. NO derivatives were measured in serum, and the expression of inducible nitric oxide synthase (iNOS), interferon (IFN-gamma), interleukin (IL-4) and epidermal Langerhans cells (LC) was measured in the lesions by immunohistology. Circulating NO concentrations, iNOS+ cell density, IFN-gamma+ Th1 cells and CD205+ Langerhans cells were higher in early lesions of resistant C57BL/6 mice. In contrast, susceptible BALB/c mice developed chronic and progressive lesions with a predominance of IL-4+ Th2 cells. In both susceptible and resistant mice, lesion size and lymph node volume followed a similar course. The early local and systemic production of NO in resistant mice may be related with the premature production of IFN-gamma observed, contributing to the resolution of the lesion.
Insights
Resistant mice control Leishmania mexicana infection through early nitric oxide (NO) and interferon-gamma (IFN-gamma) production, while susceptible mice develop chronic disease with interleukin-4 (IL-4).
Area of Science:
- Immunology
- Parasitology
- Molecular Biology
Background:
- Leishmania mexicana infection presents varying outcomes in different mouse strains.
- Understanding the immune response, including nitric oxide (NO) and cytokine patterns, is crucial for predicting infection course.
Purpose of the Study:
- To investigate the roles of NO and cytokine profiles in BALB/c (susceptible) and C57BL/6 (resistant) mice during Leishmania mexicana infection.
- To correlate immune responses with lesion development and resolution.
Main Methods:
- Measurement of NO derivatives in serum.
- Immunohistological analysis of inducible nitric oxide synthase (iNOS), IFN-gamma, IL-4, and Langerhans cells (LC) in lesions.
- Comparison of immune markers and lesion progression in susceptible and resistant mouse models.
Main Results:
- Resistant C57BL/6 mice exhibited higher early levels of NO, iNOS, IFN-gamma (Th1 cells), and Langerhans cells in lesions.
- Susceptible BALB/c mice showed a predominance of IL-4 (Th2 cells) and developed chronic, progressive lesions.
- Lesion size and lymph node volume progression were similar in both strains despite differing immune responses.
Conclusions:
- Early local and systemic NO production in resistant mice is linked to premature IFN-gamma production.
- This early immune response in resistant mice may contribute to the resolution of Leishmania mexicana lesions.
- Distinct cytokine profiles (Th1 vs. Th2) dictate the outcome of Leishmania mexicana infection in mice.
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