Regulation of Leishmania (L.) amazonensis Protein Expression by Host T Cell Dependent Responses: Differential Expression of Oligopeptidase B, Tryparedoxin Peroxidase and HSP70 Isoforms in Amastigotes Isolated from BALB/c and BALB/c Nude Mice

Abstract

Leishmaniasis is an important disease that affects 12 million people in 88 countries, with 2 million new cases every year. Leishmania amazonensis is an important agent in Brazil, leading to clinical forms varying from localized (LCL) to diffuse cutaneous leishmaniasis (DCL). One interesting issue rarely analyzed is how host immune response affects Leishmania phenotype and virulence. Aiming to study the effect of host immune system on Leishmania proteins we compared proteomes of amastigotes isolated from BALB/c and BALB/c nude mice. The athymic nude mice may resemble patients with diffuse cutaneous leishmaniasis, considered T-cell hyposensitive or anergic to Leishmania´s antigens. This work is the first to compare modifications in amastigotes’ proteomes driven by host immune response. Among the 44 differentially expressed spots, there were proteins related to oxidative/nitrosative stress and proteases. Some correspond to known Leishmania virulence factors such as OPB and tryparedoxin peroxidase. Specific isoforms of these two proteins were increased in parasites from nude mice, suggesting that T cells probably restrain their posttranslational modifications in BALB/c mice. On the other hand, an isoform of HSP70 was increased in amastigotes from BALB/c mice. We believe our study may allow identification of potential virulence factors and ways of regulating their expression.

Comparative genomics of Tunisian Leishmania major isolates causing human cutaneous leishmaniasis with contrasting clinical severity

“…These proteins are known to have chaperone function upon stress conditions in amastigotes (Morales et al, 2010). Strikingly, genes such as heat shock proteins, tryparedoxin, or the tryparedoxin peroxidase related to oxidative/nitrosative stress (Teixeira et al, 2015) and known as virulence factors (Iyer et al, 2008), showed missing copies compared to the reference genome, although differentially present between our two isolates. Interestingly, the ATP-binding cassette protein subfamily A (ABCA) showed an expansion of gene copies in the 2938_HV genome.…”

Proteomics and Leishmaniasis: Potential Clinical Applications

“…Human infections by L. amazonensis usually lead to LCL, and more rarely to DCL. DCL patients are anergic to Leishmania antigens, lesions are not ulcerated and have higher parasite loads, similar to nude mice lesions . Other study showed that parasites isolated from human DCL infect more macrophages and develop larger vacuoles relative to LCL .…”

“…TXNPx has been associated with virulence in different species of Leishmania . Indeed, our group compared amastigotes of L. amazonensis isolated from lesions of immunocompetent and immunodeficient nude mice and identified isoforms of TXNPx and oligopeptidase B (OPB) more abundant in parasites from nude mice . Nude derived amastigotes were more virulent in second infections in mice when compared with BALB/c's (Stolf et al., personal communication), suggesting that TXNPx and OPB may be involved in increased virulence.…”

HSP70 of Leishmania amazonensis alters resistance to different stresses and mitochondrial bioenergetics

“…To date, studies have focused on the L. amazonensis sequence and genomic organisation of HSP70, as well as its identification ( Teixeira et al 2015 ) and detection ( Araújo & Giorgio 2015 ). The biological role of HSP70 in this parasite species and its involvement in energy metabolism has not yet been investigated.…”