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Toll-like receptor 4 polymorphisms predispose to cutaneous leishmaniasis

Soheila Ajdary1, Mir-Mostafa Ghamilouie, Mohammad-Hossein Alimohammadian

  • 1Immunology Department, Pasteur Institute of Iran, Pasteur Ave., Tehran, Islamic Republic of Iran. sohary@yahoo.com

Microbes and Infection
|November 9, 2010
PubMed

Insights

Toll-like receptor 4 (TLR4) gene mutations are linked to increased susceptibility and severity of cutaneous leishmaniasis (CL). Specific TLR4 variants, Asp299Gly and Thr399Ile, were found more frequently in patients with acute and chronic CL, indicating a role in disease outcome.

Area of Science:

  • Immunogenetics
  • Infectious Diseases
  • Dermatology

Background:

  • Cutaneous leishmaniasis (CL) presents with highly variable clinical manifestations.
  • Toll-like receptor 4 (TLR4) has been implicated in controlling leishmaniasis infections in experimental models.

Purpose of the Study:

  • To investigate the association between specific Toll-like receptor 4 (TLR4) gene mutations (Asp299Gly and Thr399Ile) and the clinical outcome of cutaneous leishmaniasis (CL).

Main Methods:

  • Genotyping was performed for TLR4 Asp299Gly and Thr399Ile mutations in patients with chronic CL (N=22), acute CL (N=61), asymptomatic individuals (N=45), and healthy controls (N=75).
  • Statistical analysis, including odds ratios (OR) and p-values, was used to compare genotype frequencies between groups.

Main Results:

  • The Asp299Gly genotype was significantly more frequent in patients with chronic CL (OR 25.3) and acute CL (OR 8.03) compared to healthy controls.
  • The Thr399Ile genotype was overrepresented in patients with chronic CL (27.3%), acute CL (13.1%), and asymptomatic individuals (15.6%) versus healthy controls (1.3%).
  • Concomitant carriage of both TLR4 mutations was more frequent in chronic CL patients than in acute CL or asymptomatic individuals.

Conclusions:

  • Polymorphisms in the TLR4 gene are associated with increased susceptibility to and severity of Leishmania major infection, leading to CL.
  • The presence of both Asp299Gly and Thr399Ile mutations in the TLR4 gene exacerbates an individual's susceptibility to cutaneous leishmaniasis.

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