Leishmania (Leishmania) amazonensis: Experimental cutaneous leishmaniasis associated with systemic amyloidosis in mice

Carvalho, Luiz Otávio Pereira; Calabrese, Kátia da Silva; Costa, Salvatore; Mendes, Verônica Gonçalves; Silva, Ana Patrícia de Carvalho da; Barros, Ana Caroline Ericeira; Melo, Solange de Araújo; Abreu-Silva, Ana Lúcia

doi:10.1016/j.exppara.2008.06.004

Cited by 8 publications

(6 citation statements)

References 10 publications

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“…The increase in size of infected footpads is a specific measure of the progress of infection since the normal increase of footpad size with corporal growth is subtracted. It might be argued that the lesion size might also be influenced by the amount and nature of the local inflammatory response [48] which might be mediated by the B2R receptor for the released bradykinin at the local of infection [49]. In Swiss and C57BL/6 mice infected with L. amazonensis , the histopatological primary footpad lesion analysis showed liquefactive necrosis and inflammatory infiltrate mainly consisting of macrophages filled with amastigotes and rare lymphocytes [48].…”

Section: Discussionmentioning

confidence: 99%

“…It might be argued that the lesion size might also be influenced by the amount and nature of the local inflammatory response [48] which might be mediated by the B2R receptor for the released bradykinin at the local of infection [49]. In Swiss and C57BL/6 mice infected with L. amazonensis , the histopatological primary footpad lesion analysis showed liquefactive necrosis and inflammatory infiltrate mainly consisting of macrophages filled with amastigotes and rare lymphocytes [48]. Interestingly, the study of the dermal ear infection with L. amazonensis in C57Bl/6 mice showed that the absence of the TLR2 receptor determined the reduction of both the parasite load and the recruitment of inflammatory cells [50].…”

Section: Discussionmentioning

confidence: 99%

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Adaptive Immunity against Leishmania Nucleoside Hydrolase Maps Its C-Terminal Domain as the Target of the CD4+ T Cell–Driven Protective Response

et al. 2010

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Nucleoside hydrolases (NHs) show homology among parasite protozoa, fungi and bacteria. They are vital protagonists in the establishment of early infection and, therefore, are excellent candidates for the pathogen recognition by adaptive immune responses. Immune protection against NHs would prevent disease at the early infection of several pathogens. We have identified the domain of the NH of L. donovani (NH36) responsible for its immunogenicity and protective efficacy against murine visceral leishmaniasis (VL). Using recombinant generated peptides covering the whole NH36 sequence and saponin we demonstrate that protection against L. chagasi is related to its C-terminal domain (amino-acids 199–314) and is mediated mainly by a CD4+ T cell driven response with a lower contribution of CD8+ T cells. Immunization with this peptide exceeds in 36.73±12.33% the protective response induced by the cognate NH36 protein. Increases in IgM, IgG2a, IgG1 and IgG2b antibodies, CD4+ T cell proportions, IFN-γ secretion, ratios of IFN-γ/IL-10 producing CD4+ and CD8+ T cells and percents of antibody binding inhibition by synthetic predicted epitopes were detected in F3 vaccinated mice. The increases in DTH and in ratios of TNFα/IL-10 CD4+ producing cells were however the strong correlates of protection which was confirmed by in vivo depletion with monoclonal antibodies, algorithm predicted CD4 and CD8 epitopes and a pronounced decrease in parasite load (90.5–88.23%; p = 0.011) that was long-lasting. No decrease in parasite load was detected after vaccination with the N-domain of NH36, in spite of the induction of IFN-γ/IL-10 expression by CD4+ T cells after challenge. Both peptides reduced the size of footpad lesions, but only the C-domain reduced the parasite load of mice challenged with L. amazonensis. The identification of the target of the immune response to NH36 represents a basis for the rationale development of a bivalent vaccine against leishmaniasis and for multivalent vaccines against NHs-dependent pathogens.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Adaptive Immunity against Leishmania Nucleoside Hydrolase Maps Its C-Terminal Domain as the Target of the CD4+ T Cell–Driven Protective Response

et al. 2010

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“…Carvalho et al (2008) reported inflammation in these same layers, but they did not observe parasites in the adrenal glands of mice experimentally infected with L. amazonensis. Toplu and Aydogan (2011) also observed the parasite in the medullary layer and, less frequently, in the cortical layer of 22.7% of the 22 dogs evaluated.…”

Section: Discussionmentioning

confidence: 99%

Morphological changes and parasite load of the adrenal from dogs with visceral leishmaniasis

Momo

Rocha

Moreira

et al. 2014

Rev. Bras. Parasitol. Vet.

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The objective of this study was to analyze morphological changes and parasite loads in the adrenal gland from 45 dogs with visceral leishmaniasis (VL). The animals were from the Zoonosis Control Center of Araçatuba, state of São Paulo, which is an endemic region for the disease. These animals were euthanized due to positive diagnoses of VL. The dogs were classified into asymptomatic, oligosymptomatic and symptomatic groups. The parasite load was determined by immunohistochemistry, using VL-positive dog hyperimmune serum. Nine dogs showed an inflammatory infiltrate composed, predominantly, of plasma cells and macrophages. However, only eight dogs showed macrophages with amastigote forms of the parasite, immunolabeled in the cytoplasm. The medullary and reticular layers were the most affected areas, possibly due to a favorable microenvironment created by hormones in these regions. The density of parasites in the glandular tissue was not associated with clinical signs of VL (P > 0.05). However, the presence of the parasite was always associated with the presence of a granulomatous inflammatory infiltrate. This gland may not be an ideal place for the parasite's multiplication, but the presence of injuries to the glandular tissue could influence the dog's immune system, thus favoring the parasite's survival in the host's different organs.Keywords: Leishmania infantum chagasi, adrenalitis, dog, immunohistochemistry. ResumoO objetivo deste estudo foi analisar as alterações morfológicas e a carga parasitária da glândula adrenal de 45 cães com leishmaniose visceral (LV). Os animais eram provenientes do Centro de Controle de Zoonoses (CCZ) de Araçatuba (SP), região endêmica para a doença. Esses animais são submetidos à eutanásia, devido ao diagnóstico positivo para LV. Os cães foram classificados nos grupos assintomático, oligossintomático e sintomático. A determinação da carga parasitária foi feita por imuno-histoquímica, com utilização de soro hiperimune de cão positivo para LV. Em nove cães, verificou-se um infiltrado inflamatório, composto predominantemente por plasmócitos e macrófagos. Entretanto, apenas oito cães apresentaram macrófagos com formas amastigotas do parasito imunomarcadas em seu citoplasma. As camadas medular e reticulada foram as mais afetadas, possivelmente por um microambiente favorável criado pelos hormônios nestas regiões. A densidade de parasitos no tecido glandular não foi relacionada com os sinais clínicos de LV (P > 0,05). No entanto, a presença do parasito sempre esteve associada à presença de infiltrado inflamatório granulomatoso. Possivelmente, essa glândula não é um sítio ideal para a multiplicação do protozoário, mas a presença de injúrias no tecido glandular poderia influenciar o sistema imune do cão, favorecendo a sobrevivência do parasito nos diferentes órgãos do hospedeiro.Palavras-chave: Leishmania infantum chagasi, adrenalite, cão, imuno-histoquímica.

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“…AA amyloidosis is rarely described in naturally infection by Leishmania spp. However several author have been reported the occurrence of this disease in experimental infection (Carvalho et al, 2008;Barbosa-Santos et al, 1984). Even in murine model it has been observed that AA amyloidosis occur only in some strains of mice.…”

Section: Amyloidosis X Leishmaniasismentioning

confidence: 99%

“…Even in murine model it has been observed that AA amyloidosis occur only in some strains of mice. In different experiment where DBA/2, Swiss, BALB/c, C57BL/6 female were infected with promastigote and amastigote of L. amanozensis just Swiss and C57BL/6 presented amyloidosis in the course of the infection (Cupolillo et al, 1998Carvalho et al, 2008. Several hypotheses have been postulated to explain why a minority of patients displayed AA amyloidosis during chronic inflammatory infection.…”

Section: Amyloidosis X Leishmaniasismentioning

confidence: 99%

Amyloidosis Associated to Leishmania Infection in Murine Model

Abreu-Silva¹,

Xavier-Silva²,

Milhomem³

et al. 2011

Amyloidosis - Mechanisms and Prospects for Therapy

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Leishmania (Leishmania) amazonensis: Experimental cutaneous leishmaniasis associated with systemic amyloidosis in mice

Cited by 8 publications

References 10 publications

Adaptive Immunity against Leishmania Nucleoside Hydrolase Maps Its C-Terminal Domain as the Target of the CD4+ T Cell–Driven Protective Response

Adaptive Immunity against Leishmania Nucleoside Hydrolase Maps Its C-Terminal Domain as the Target of the CD4+ T Cell–Driven Protective Response

Morphological changes and parasite load of the adrenal from dogs with visceral leishmaniasis

Amyloidosis Associated to Leishmania Infection in Murine Model

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