In the Leishmania major mouse model of cutaneous leishmaniasis inducible nitric oxide synthase (iNOS) is crucial for the killing of the parasite in the skin and draining lymph node. However, the effector mechanism operating against L. major in the spleen is unknown. As reactive oxygen intermediates might play a role, we analyzed macrophages and mice lacking the gp91phox subunit of the phagocyte NADPH oxidase (phox) for their ability to combat an infection with L. major. Macrophages from wild-type and gp91phox -/-mice had an equal capacity to kill L. major after activation by cytokines. Unlike iNOS, the activity of phox was dispensable for the resolution of the acute skin lesions and exerted only a limited effect on the containment of the parasites in the draining lymph node, but was essential for the clearance of L. major in the spleen. During the chronic phase of infection, parasites persisted at high levels in gp91phox -/-mice, and cutaneous lesions re-emerged in approximately 60% of these mice. gp91phox deficiency did not impair the expression of iNOS or the production of TNF and IFN-+ . These results demonstrate that iNOS and phox are both required for the control of L. major in vivo and display unexpected organ-and stage-specific anti-leishmanial effects.
Cutaneous leishmaniasis is caused by protozoan parasites of the genusParasites of the protozoan genus Leishmania are transmitted by sandflies to mammalian hosts, including humans, in which they elicit a spectrum of diseases that range from cutaneous to mucocutaneous and visceral leishmaniasis (48). One key factor that determines the clinical manifestation and course of infection is the parasite species. Thus, local cutaneous leishmaniasis is caused by Leishmania (subgenus Leishmania) major and L. (L.) tropica in Europe and the Near and Far East and by Leishmania (subgenus Viannia) braziliensis, L. (V.) guyanensis, and Leishmania (L.) mexicana in the Americas, whereas the prototypic species associated with visceral leishmaniasis are Leishmania (L.) donovani, Leishmania (L.) infantum, and (L.) chagasi (18,66)
A leishmaniose é uma doença negligenciada que está entre as cinco doenças infecto-parasitárias endêmicas de maior relevância. O trabalho teve por objetivo analisar a frequência e o perfil epidemiológico e sociodemográfico dos pacientes com Leishmaniose Tegumentar Americana e acompanhar as medidas de controle. Trata-se de um estudo quantitativo de caráter retrospectivo. Do total dos pacientes acometidos, verificou-se que 59,4% deles eram do sexo masculino, 33,5% possuíam idade menor do que 12 anos, 83,1 % eram pardos e 79,3% estudaram até o ensino fundamental incompleto. Observou-se que a maioria dos diagnósticos para leishmaniose tegumentar americana é emitido baseando-se apenas pelo critério clínico epidemiológico, tendo em vista que os exames parasitológicos e imunológicos foram raramente utilizados para diagnóstico. O maior foco da doença concentrou-se nas áreas de abrangência da Unidade da Saúde da Família (USF) do Imbu, correspondendo a 79,3% dos casos. Em relação às medidas de controle, observou-se que 69,2% dos profissionais possuíam conhecimentos sobre leishmaniose, 84,6% das unidades de saúde da família não desenvolviam programas de ação e estratégias, 76,9% dos profissionais não participaram de atividades educativas na comunidade, porém, há divulgação à população sobre a ocorrência dos casos de LTA (69,2%). Apesar da alta frequência da ocorrência de leishmaniose tegumentar americana no município, as USFs não estavam atuantes no que concernem as medidas de controle referente ao agravo e não participavam de programas de educação em saúde.
Imaging mass spectrometry (IMS) is recognized as a powerful tool to investigate the spatial distribution of untargeted or targeted molecules of a wide variety of samples including tissue sections. Leishmania is a protozoan parasite that causes different clinical manifestations in mammalian hosts. Leishmaniasis is a major public health risk in different continents and represents one of the most important neglected diseases. Cutaneous lesions from mice experimentally infected with Leishmania spp. were investigated by matrix-assisted laser desorption ionization MS using the SCiLS Lab software for statistical analysis. Being applied to cutaneous leishmaniasis (CL) for the first time, MALDI-IMS was used to search for peptides and low molecular weight proteins (2-10 kDa) as candidates for potential biomarkers. Footpad sections of Balb/c mice infected with (i) Leishmania amazonensis or (ii) Leishmania major were imaged. The comparison between healthy and infected skin highlighted a set of twelve possible biomarker proteins for L. amazonenis and four proteins for L. major. Further characterization of these proteins could reveal how these proteins act in pathology progression and confirm their values as biomarkers.
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