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The wound repair response controls outcome to cutaneous leishmaniasis

Anuratha Sakthianandeswaren1, Colleen M Elso, Ken Simpson

  • 1Genetics and Bioinformatics Division, The Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3050, Australia.

Proceedings of the National Academy of Sciences of the United States of America
|October 15, 2005
PubMed

Insights

Rapid wound healing is crucial for curing leishmaniasis infections. Enhanced tissue repair mechanisms, independent of T cell immunity, contribute to innate resistance against this parasitic disease.

Area of Science:

  • Immunology
  • Parasitology
  • Wound Healing Research

Background:

  • Chronic microbial infections, like leishmaniasis, involve granulomas resembling wound-healing processes.
  • Susceptibility to leishmaniasis is influenced by genetic loci (lmr1, lmr2, lmr3) acting independently of T cell responses.

Purpose of the Study:

  • To investigate the role of wound repair mechanisms in the resolution of murine cutaneous leishmaniasis.
  • To determine if enhanced wound healing contributes to innate immunity against Leishmania major.

Main Methods:

  • Comparative analysis of lesion cure rates in congenic mice with differing leishmaniasis resistance loci.
  • Gene expression profiling of tissue repair-related genes in resistant versus susceptible mice.
  • Assessment of collagen organization and punch biopsy wound healing times.
  • In vitro fibroblast wound repair assays using supernatants from infected macrophages.

Main Results:

  • Mice with leishmaniasis resistance loci exhibited faster lesion cure and quicker punch biopsy wound healing.
  • Resistant mice showed differential expression of tissue repair genes and more organized collagen deposition.
  • Fibroblast repair of in vitro wounds was accelerated in cells from resistant mice.
  • Macrophage supernatants enhanced fibroblast wound repair, indicating a role for innate immune mediators.

Conclusions:

  • The rate of wound healing is a significant factor in the innate immune response to cutaneous leishmaniasis.
  • Enhanced tissue repair mechanisms contribute to resistance and rapid cure of Leishmania major infections.
  • Genetic control of wound repair processes plays a critical role in leishmaniasis outcome, independent of adaptive immunity.

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