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A2 and Other Visceralizing Proteins of Leishmania: Role in Pathogenesis and Application for Vaccine Development

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Part of the book series: Subcellular Biochemistry ((SCBI,volume 74))

Abstract

Visceral leishmaniasis is a re-emergent disease and a significant cause of morbidity worldwide. Amongst the more than 20 Leishmania species, Leishmania donovani, Leishmania infantum and more rarely Leishmania amazonensis are associated with visceral leishmaniasis. A major question in leishmaniasis research is how these species migrate to and infect visceral organs whereas other species such as Leishmania major and Leishmania braziliensis remain in the skin, causing tegumentary leishmaniasis. Here we present the more recent advances and approaches towards the identification of species-specific visceralizing factors of Leishmania, such as the A2 protein, leading to a better understanding of parasite biology. We also discuss their potential use for the development of a vaccine for visceral leishmaniasis.

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Abbreviations

cGAPDH:

Cytosolic GAPDH

CL:

Cutaneous leishmaniasis

CTL:

Cytolytic T lymphocytes

CVL:

Canine visceral leishmaniasis

DALYs:

Disability-adjusted life years

DCL:

Diffuse cutaneous leishmaniasis

DCs:

Dendritic cells

DHFR-TS:

Dihydrofolate reductase-thymidilate synthase

ELISA:

Enzyme-linked immunosorbent assay

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

gp:

Glycoprotein

hsp:

Heat shock protein

IFN-γ:

Gamma interferon

Ig:

Immunoglobulin

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

MHC:

Major histocompatibility complex

ML:

Mucosal leishmaniasis

mo-DCs:

Monocyte-derived dendritic cells

mRNA:

Messenger ribonucleic acid

NK:

Natural killer

PCR:

Polimerase chain reaction

PKDL:

Post-kala azar dermal leishmaniasis

RNI:

Radical nitrogen intermediates

ROI:

Radical oxygen intermediates

SIDER:

Small interspersed degenerate retroposons

TAP:

Transporter associated with antigen processing

TGF-β:

Transforming growth factor-beta

Th:

T helper

TNF-α:

Tumor Necrosis factor-alfa

Treg:

Regulatory T cells

UPR:

Unfolded protein response

UTR:

Untranslated region

VL:

Visceral leishmaniasis

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Acknowledgments

The authors thank Dr. Stephen M. Beverley from the Washington University School of Medicine for helpful discussions and permission to use unpublished phylogenetic tree topology of DHFR-TS gene sequences among the Leishmania species.

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Correspondence to Ana Paula Fernandes .

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Fernandes, A.P., Canavaci, A.M.C., McCall, LI., Matlashewski, G. (2014). A2 and Other Visceralizing Proteins of Leishmania: Role in Pathogenesis and Application for Vaccine Development. In: Santos, A., Branquinha, M., d’Avila-Levy, C., Kneipp, L., Sodré, C. (eds) Proteins and Proteomics of Leishmania and Trypanosoma. Subcellular Biochemistry, vol 74. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7305-9_3

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