Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production

Anselmo S Souza; Angela Giudice; Júlia MB Pereira; Luís H Guimarães; Amelia R de Jesus; Tatiana R de Moura; Mary E Wilson; Edgar M Carvalho; Roque P Almeida

doi:10.1186/1471-2334-10-209

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Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production

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Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production

Anselmo S Souza, Angela Giudice, Júlia MB Pereira, Luís H Guimarães, Amelia R de Jesus, Tatiana R de Moura, Mary E Wilson, Edgar M Carvalho and Roque P Almeida

BMC infectious diseases, Vol.10(1), pp.209-209

07/15/2010

DOI: 10.1186/1471-2334-10-209

PMCID: PMC2915995

PMID: 20633260

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Abstract

Background Nitric oxide (NO) produced in macrophages plays a pivotal role as a leishmanicidal agent. A previous study has demonstrated that 20% of the L. (V.) braziliensis isolated from initial cutaneous lesions of patients from the endemic area of Corte de Pedra, Bahia, Brazil, were NO resistant. Additionally, 5 to 11% of the patients did not respond to three or more antimony treatments" (refractory patients). The aim of this study is to investigate if there is an association between the resistance of L. (V.) braziliensis to NO and nonresponsiveness to antimony therapy and cytokine production. Methods We evaluated the in vitro toxicity of NO against the promastigotes stages of L. (V.) braziliensis isolated from responsive and refractory patients, and the infectivity of the amastigote forms of these isolates against human macrophages. The supernatants from Leishmania infected macrophage were used to measure TNF-α and IL-10 levels. Results Using NaNO2 (pH 5.0) as the NO source, L. (V.) braziliensis isolated from refractory patients were more NO resistant (IC50 = 5.8 ± 4.8) than L. (V.) braziliensis isolated from responsive patients (IC50 = 2.0 ± 1.4). Four isolates were selected to infect human macrophages: NO-susceptible and NO-resistant L. (V.) braziliensis isolated from responsive and refractory patients. NO-resistant L. (V.) braziliensis isolated from refractory patients infected more macrophages stimulated with LPS and IFN-γ at 120 hours than NO-susceptible L. (V.) braziliensis isolated from refractory patients. Also, lower levels of TNF-α were detected in supernatants of macrophages infected with NO-resistant L. (V.) braziliensis as compared to macrophages infected with NO-susceptible L. (V.) braziliensis (p < 0.05 at 2, 24 and 120 hours), while no differences were detected in IL-10 levels. Conclusion These data suggest that NO resistance could be related to the nonresponsiveness to antimony therapy seen in American Tegumentary Leishmaniasis.

Details

Title: Subtitle: Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production
Creators: Anselmo S Souza - Departments of Internal Medicine, Microbiology and Epidemiology, University of Iowa and the VA Medical Center, Iowa City, IA, USA
Angela Giudice - Departments of Internal Medicine, Microbiology and Epidemiology, University of Iowa and the VA Medical Center, Iowa City, IA, USA
Júlia MB Pereira - Departments of Internal Medicine, Microbiology and Epidemiology, University of Iowa and the VA Medical Center, Iowa City, IA, USA
Luís H Guimarães - Departments of Internal Medicine, Microbiology and Epidemiology, University of Iowa and the VA Medical Center, Iowa City, IA, USA
Amelia R de Jesus - Departments of Internal Medicine, Microbiology and Epidemiology, University of Iowa and the VA Medical Center, Iowa City, IA, USA
Tatiana R de Moura - Departments of Internal Medicine, Microbiology and Epidemiology, University of Iowa and the VA Medical Center, Iowa City, IA, USA
Mary E Wilson - Departments of Internal Medicine, Microbiology and Epidemiology, University of Iowa and the VA Medical Center, Iowa City, IA, USA
Edgar M Carvalho - Departments of Internal Medicine, Microbiology and Epidemiology, University of Iowa and the VA Medical Center, Iowa City, IA, USA
Roque P Almeida - Departments of Internal Medicine, Microbiology and Epidemiology, University of Iowa and the VA Medical Center, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: BMC infectious diseases, Vol.10(1), pp.209-209
DOI: 10.1186/1471-2334-10-209
PMID: 20633260
PMCID: PMC2915995
NLM abbreviation: BMC Infect Dis
ISSN: 1471-2334
eISSN: 1471-2334
Publisher: BioMed Central
Language: English
Date published: 07/15/2010
Academic Unit: Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
Record Identifier: 9984001214602771

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