Leishmania (L.) amazonensis LaLRR17 increases parasite entry in macrophage by a mechanism dependent on GRP78

Autor: Mauricio S. Peña, Fenny Hui Fen Tang, Fernando Alves de Lima Franco, Alessandro Taunay Rodrigues, Guilherme Moreira Paiva Carrara, Thaís Larissa Silva Araujo, Ricardo José Giordano, Giuseppe Palmisano, Maristela Martins de Camargo, Silvia Reni Bortolin Uliana, Beatriz Simonsen Stolf
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Parasitology, Vol 150, Pp 922-933 (2023)
Druh dokumentu: article
ISSN: 00311820
0031-1820
1469-8161
48482331
DOI: 10.1017/S0031182023000720
Popis: Leishmaniases affect 12 million people worldwide. They are caused by Leishmania spp., protozoan parasites transmitted to mammals by female phlebotomine flies. During the life cycle, promastigote forms of the parasite live in the gut of infected sandflies and convert into amastigotes inside the vertebrate macrophages. The parasite evades macrophage's microbicidal responses due to virulence factors that affect parasite phagocytosis, survival and/or proliferation. The interaction between Leishmania and macrophage molecules is essential to phagocytosis and parasite survival. Proteins containing leucine-rich repeats (LRRs) are common in several organisms, and these motifs are usually involved in protein–protein interactions. We have identified the LRR17 gene, which encodes a protein with 6 LRR domains, in the genomes of several Leishmania species. We show here that promastigotes of Leishmania (L.) amazonensis overexpressing LaLRR17 are more infective in vitro. We produced recombinant LaLRR17 protein and identified macrophage 78 kDa glucose-regulated protein (GRP78) as a ligand for LaLRR17 employing affinity chromatography followed by mass spectrometry. We showed that GRP78 binds to LaLRR17 and that its blocking precludes the increase of infection conferred by LaLRR17. Our results are the first to report LRR17 gene and protein, and we hope they stimulate further studies on how this protein increases phagocytosis of Leishmania.
Databáze: Directory of Open Access Journals