Resistance of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis to nitric oxide correlates with disease severity in Tegumentary Leishmaniasis
1 Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Instituto de Investigação em Imunologia (iii), Universidade Federal da Bahia, Salvador, Bahia, Brazil
2 Departamento de Fisiologia, Universidade Federal de Sergipe, Aracaju, Sergipe, Brazil
3 Division of Infectious Diseases, School of Public Health, University of California, Berkeley, CA, USA
4 Department of Internal Medicine, Microbiology, University of Iowa College of Medicine, Iowa City, IA, USA
5 Department of Medicine, Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University, New York, NY, USA
BMC Infectious Diseases 2007, 7:7 doi:10.1186/1471-2334-7-7Published: 22 February 2007
Nitric oxide (NO•) plays a pivotal role as a leishmanicidal agent in mouse macrophages. NO• resistant Escherichia coli and Mycobacterium tuberculosis have been associated with a severe outcome of these diseases.
In this study we evaluated the in vitro toxicity of nitric oxide for the promastigote stages of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis parasites, and the infectivity of the amastigote stage for human macrophages. Parasites were isolated from patients with cutaneous, mucosal or disseminated leishmaniasis, and NO• resistance was correlated with clinical presentation.
Seventeen isolates of L. (L.) amazonensis or L. (V.) braziliensis promastigotes were killed by up to 8 mM of more of NaNO2 (pH 5.0) and therefore were defined as nitric oxide-susceptible. In contrast, eleven isolates that survived exposure to 16 mM NaNO2 were defined as nitric oxide-resistant. Patients infected with nitric oxide-resistant Leishmania had significantly larger lesions than patients infected with nitric oxide-susceptible isolates. Furthermore, nitric oxide-resistant L. (L.) amazonensis and L. (V.) braziliensis multiplied significantly better in human macrophages than nitric oxide-susceptible isolates.
These data suggest that nitric oxide-resistance of Leishmania isolates confers a survival benefit for the parasites inside the macrophage, and possibly exacerbates the clinical course of human leishmaniasis.