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Arginase I induction during Leishmania major infection mediates the development of disease

Virginia Iniesta1, Jesualdo Carcelén, Isabel Molano

  • 1Facultad de Veterinaria, Universidad de Extremadura. Avda. de la Universidad s/n, Cáceres 10071, Spain.

Infection and Immunity
|August 23, 2005
PubMed

Insights

Arginase I is induced during Leishmania infection in mice, influencing parasite replication. Its expression patterns and inhibition offer insights into disease progression and potential therapeutic strategies for leishmaniasis.

Area of Science:

  • Immunology
  • Parasitology
  • Molecular Biology

Background:

  • Arginase I induction was previously shown to enhance Leishmania replication within macrophages.
  • Understanding arginase I's role in Leishmania major infection is crucial for developing effective treatments.

Purpose of the Study:

  • To analyze the differential expression of arginase I in a mouse model of Leishmania major infection.
  • To investigate the role of arginase I in disease development and outcome in susceptible (BALB/c) and resistant (C57BL/6) mouse strains.

Main Methods:

  • Differential expression analysis of arginase I in infected mouse tissues.
  • Investigating the influence of cytokines (interleukin-4 and interleukin-12) on arginase I induction.
  • Assessing the impact of arginase inhibition and l-ornithine treatment on parasite load and disease progression.

Main Results:

  • Arginase I is upregulated in both BALB/c and C57BL/6 mice during leishmaniasis.
  • Arginase I induction kinetics differ between susceptible (parallels infection) and resistant (footpad swelling) mice.
  • Arginase I expression is modulated by the balance of interleukin-4 and interleukin-12, inversely correlating with nitric oxide synthase II.
  • Arginase inhibition reduced parasite numbers and delayed disease in BALB/c mice.
  • L-ornithine treatment increased susceptibility in C57BL/6 mice.

Conclusions:

  • Host arginase I induction is a significant factor in the pathogenesis of Leishmania major infection.
  • Arginase I expression patterns can serve as a marker for disease progression in leishmaniasis.
  • Modulating arginase I activity presents a potential therapeutic target for leishmaniasis treatment.

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