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Infection and Immunity, May 2009, p. 2022-2029, Vol. 77, No. 5
0019-9567/09/$08.00+0 doi:10.1128/IAI.01513-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Immunological Determinants of Clinical Outcome in Peruvian Patients with Tegumentary Leishmaniasis Treated with Pentavalent Antimonials 
,
Anne Maurer-Cecchini,1,2
Saskia Decuypere,3
François Chappuis,1
Coralie Alexandrenne,1,2
Simonne De Doncker,3
Marleen Boelaert,3
Jean-Claude Dujardin,3
Louis Loutan,1
Jean-Michel Dayer,2
Gianfranco Tulliano,4
Jorge Arevalo,4
Alexandro Llanos-Cuentas,4 and
Carlo Chizzolini2*
Travel and Migration Medicine Unit, University Hospital and School of Medicine, Geneva, Switzerland,1 Immunology and Allergy, University Hospital and School of Medicine, Geneva, Switzerland,2 Molecular Parasitology and Epidemiology Units, Institute of Tropical Medicine, Antwerp, Belgium,3 Laboratory of Molecular Parasitology, Instituto de Medicina Tropical Alexander von Humboldt, Lima, Peru4
Received 13 December 2008/ Returned for modification 13 January 2009/ Accepted 17 February 2009
The mechanisms linking the immune response to cutaneous and mucosal leishmaniasis (CL and ML, respectively) lesions and the response to treatment are incompletely understood. Our aims were to prospectively assess, by quantitative reverse transcription-PCR, the levels of mRNA for gamma interferon, tumor necrosis factor alpha, interleukin-10 (IL-10), IL-4, and IL-13, as well as the presence of T cells (CD2) and macrophages (CD68), in CL and ML lesions and to follow their changes in response to treatment with pentavalent antimonials. The leishmanin skin test (LST) was performed on all CL and ML patients before treatment. The patient population included individuals living in areas of Peru where the disease is endemic, i.e., 129 with CL and 43 with ML. Compared to CL patients, the LST induration size was larger, the levels of all cytokine mRNAs but IL-10 were higher, T-cell mRNA was similar, and macrophage mRNA was lower in ML patients. The proportion of CL patients with an LST induration size of >8 mm was higher among responders to treatment. In CL, the pretreatment levels of cytokine mRNAs did not discriminate between responders and nonresponders; however, treatment was more often accompanied by a reduction in the levels of T-cell and cytokine mRNAs in responders than in nonresponders. Furthermore, the production of cytokines per T cell and macrophage decreased with treatment but IL-10 production remained high in nonresponders. Overall, these findings point to complex relationships among New World Leishmania parasites, skin and mucosal immune responses, and treatment outcome. The persistence of high levels of IL-10 in CL is characteristically associated with a poor response to treatment.
* Corresponding author. Mailing address: Immunology & Allergy, Geneva University Hospital, 1211 Geneva 14, Switzerland. Phone: 41 22 372 9370. Fax: 41 22 372 9418. E-mail: carlo.chizzolini{at}unige.ch
Published ahead of print on 23 February 2009.
Anne Maurer-Cecchini passed away in March 2006. Her enthusiasm and dedication were the soul and principal force behind this paper.
Infection and Immunity, May 2009, p. 2022-2029, Vol. 77, No. 5
0019-9567/09/$08.00+0 doi:10.1128/IAI.01513-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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