Amyloidosis in Experimental Tegumentary Leishmaniasis in Mice *

Barbosa-Santos, Elizabeth Gloria Oliveira; Costa, Salvatore; Alencar, Alexandre

doi:10.4269/ajtmh.1984.33.1270

Cited by 5 publications

(1 citation statement)

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“…Target genes for APP as an upstream regulator include genes ( ACTA2, BCL2, FN1, JUN, MMP1, MYC, TP53 ) identified as major hub genes in the network analysis. Systemic perturbation of the amyloid pathway has long been considered a feature of pathogenesis in leishmaniasis, contributing to inflammation in liver, spleen and kidney . Of particular interest too is the potential for identifying classes of exogenous chemical compounds that might point the way to potential new drugs to achieve the same effect, but improve on, SSG.…”

Section: Discussionmentioning

confidence: 99%

Expression profiling of Sudanese visceral leishmaniasis patients pre‐ and post‐treatment with sodium stibogluconate

Salih

Fakiola

Lyons

et al. 2017

Parasite Immunology

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Summary Visceral leishmaniasis (VL) in Sudan caused by Leishmania donovani is fatal in susceptible individuals if untreated. Treatment with sodium stibogluconate (SSG) leads to post‐kala‐azar dermal leishmaniasis (PKDL) in 58% of patients. Here, Affymetrix microarrays were used to identify genes differentially expressed in lymph nodes (N=9 paired samples) pre‐ and post‐treatment with SSG. Using the Bioconductor package limma, 438 genes from 28 869 post‐quality‐control probe sets were differentially expressed (Pnominal≤.02) post‐ vs pretreatment. Canonical pathway analysis using Ingenuity Pathway Analysis™ identified “role of nuclear factor of activated T‐cell in regulation of immune response” (Pnominal=1.35×10−5; PBH‐adjusted=4.79×10−3), “B‐cell development” (Pnominal=2.04×10−4; PBH‐adjusted=.024), “Fcγ receptor‐mediated phagocytosis in macrophages and monocytes” (Pnominal=2.04×10−4; PBH‐adjusted=.024) and “OX40 signalling” (Pnominal=2.82×10−4; PBH‐adjusted=.025) as pathways differentially regulated post‐ vs pretreatment. Major network hub genes included TP53, FN1, MYC, BCL2, JUN, SYK, RUNX2, MMP1 and ACTA2. Top endogenous upstream regulators included IL‐7 (P=2.28×10−6), TNF (P=4.26×10−6), Amyloid Precursor Protein (P=4.23×10−5) and SPI1/PI.1 (P=1.17×10−7). Top predicted chemical drug regulators included the flavonoid genistein (P=4.56×10−7) and the quinoline alkaloid camptothecin (P=5.14×10−5). These results contribute to our understanding of immunopathology associated with VL and response to SSG treatment. Further replication could identify novel therapeutic strategies that improve on SSG treatment and reduce the likelihood of progression to PKDL.

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Section: Discussionmentioning

confidence: 99%

Expression profiling of Sudanese visceral leishmaniasis patients pre‐ and post‐treatment with sodium stibogluconate

Salih

Fakiola

Lyons

et al. 2017

Parasite Immunology

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

Carvalho

Calabrese

Costa

et al. 2008

Experimental Parasitology

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Late Cutaneous Metastases in C3H SCID Mice Infected with Leishmania amazonensis

Vanloubbeeck

Ackermann

Jones

2005

Journal of Parasitology

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The biological behavior of Leishmania amazonensis in the mammalian host is highly variable, resulting in local to diffuse cutaneous lesions that sometimes metastasize. Inflammation and, more specifically, CD4+ T cells have been shown to enhance metastases in mice infected with L. amazonensis, suggesting that the process may be lymphocyte mediated. However, we document, in this study, the development of multiple cutaneous metastases in C3H SCID mice infected with L. amazonensis. This shows that functional T and B cells are not required for metastases to occur.

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Amyloidosis in Experimental Tegumentary Leishmaniasis in Mice *

Cited by 5 publications

References 0 publications

Expression profiling of Sudanese visceral leishmaniasis patients pre‐ and post‐treatment with sodium stibogluconate

Expression profiling of Sudanese visceral leishmaniasis patients pre‐ and post‐treatment with sodium stibogluconate

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

Late Cutaneous Metastases in C3H SCID Mice Infected with Leishmania amazonensis

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