The genetics of Leishmania virulence

Abstract

The ability of Leishmania parasites to infect and persist in the antigen-presenting cell population of their mammalian hosts is dependent on their ability to gain entry to their host and host cells, to survive the mammalian cell environment, and to suppress or evade the protective immune response mechanisms of their hosts. A multitude of genes and their products have been implicated in each of these virulence-enhancing strategies to date, and we present an overview of the nature and known function of such virulence genes.

In vitro antileishmanial activity of Mexican medicinal plants

“…Leishmaniases can be classified into three main types, according to its clinical manifestations: cutaneous (CL), which affects only localized parts of the skin and is the most common form of the disease; mucocutaneous (MCL), which has the ability to destroy mucous tissue and is exclusively present in America; and visceral (VL) which is the less common type of leishmaniasis but causes liver and spleen distention and can be fatal if it does not receive prompt treatment ( Akhoundi et al, 2016 ; Bifeld and Clos, 2015 ). Leishmaniases, as in other countries, are endemic maladies of Mexico.…”

“…The main chemotherapeutic treatment against leishmaniases are drugs based on pentavalent antimony ( Bifeld and Clos, 2015 ). However, these drugs have cardiotoxic, hepatotoxic, and nephrotoxic side effects ( Sundar and Chakravarty, 2010 ).…”

Apoptotic induction inducesLeishmania aethiopicaandL. mexicanaspreading in terminally differentiated THP-1 cells

“…Survival inside host macrophages depends on the ability of well characterized virulence factors (e.g. GIPLs, GP63, LPG, PPG and KMP-11) to inhibit macrophages anti-microbial activity (Bifeld and Clos, 2015). Leishmania inhibits multiple host pathways including lysosomal fusion (Lodge and Descoteaux, 2005), inflammatory cytokine and chemokine production (Cameron et al 2004;Gregory et al 2008), and MHC class II expression (De Souza et al 1995).…”

Estudo dos efeitos da proteína LaLRR17 de >i<Leishmania (L.) amazonensis >/i<na infecção do macrófago e identificação de seus possíveis ligantes.>i<

“…A GP63 facilita a infecção e a sobrevivência de Leishmania, uma vez que degrada a matriz extracelular, aumenta a atividade da fosfatase em macrófagos infectados e aumenta a resistência a peptídeos antimicrobianos. Além disso, GP63 cliva C3 a C3b e C3bi, aumentando a resistência do parasita à lise mediada pelo complemento, e cliva diretamente os fatores pró-inflamatórios AP-1 e NF-κB (ISNARD et al,2012;BIFELD, CLOS, 2015). Enquanto alguns fatores de virulência são restritos à superfície do parasita, outros podem ser secretados.…”

“…Esses fatores de virulência têm papéis tanto dentro do parasita quanto no hospedeiro (BIFELD;CLOS, 2015).Muitos dos fatores de virulência apresentam um padrão de expressão diferencial de acordo com a fase do parasita. Dois genes fase-regulados mais expressos em promastigotas metacíclicos do que em procíclicos e amastigotas foram identificados no cromossomo 17 pelo grupo da Professora Silvia Uliana, sendo denominados META 1 e META 2.…”