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Comparative Analysis of the Secretome and Interactome of Trypanosoma cruzi and Trypanosoma rangeli Reveals Species Specific Immune Response Modulating Proteins

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Watanabe Costa, Renata [1] ; Batista, Marina Ferreira [2] ; Meneghelli, Isabela [2] ; Vidal, Ramon Oliveira [3, 4] ; Najera, Carlos Alcides [2] ; Mendes, Ana Clara [2] ; Andrade-Lima, Izabela Augusta [2] ; da Silveira, Jose Franco [1] ; Lopes, Luciano Rodrigo [5] ; Ferreira, Ludmila Rodrigues Pinto [6] ; Antoneli, Fernando [5] ; Bahia, Diana [1, 2]
Número total de Autores: 12
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, Sao Paulo - Brazil
[2] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Genet Ecol & Evolucao, Belo Horizonte, MG - Brazil
[3] Lab Nacl Biociencias LNBio, Campinas, SP - Brazil
[4] Helmholtz Assoc Berlin, Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Berlin - Germany
[5] Univ Fed Sao Paulo, Dept Informat Saude, Sao Paulo - Brazil
[6] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Morfol, RNA Syst Biol Lab RSBL, Belo Horizonte, MG - Brazil
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: FRONTIERS IN IMMUNOLOGY; v. 11, AUG 27 2020.
Citações Web of Science: 0

Chagas disease, a zoonosis caused by the flagellate protozoanTrypanosoma cruzi, is a chronic and systemic parasitic infection that affects similar to 5-7 million people worldwide, mainly in Latin America. Chagas disease is an emerging public health problem due to the lack of vaccines and effective treatments. According to recent studies, severalT. cruzisecreted proteins interact with the human host during cell invasion. Moreover, some comparative studies withT. rangeli, which is non-pathogenic in humans, have been performed to identify proteins directly involved in the pathogenesis of the disease. In this study, we present an integrated analysis of canonical putative secreted proteins (PSPs) from both species. Additionally, we propose an interactome with human host and gene family clusters, and a phylogenetic inference of a selected protein. In total, we identified 322 exclusively PSPs inT. cruziand 202 inT. rangeli. Among the PSPs identified inT. cruzi, we found several trans-sialidases, mucins, MASPs, proteins with phospholipase 2 domains (PLA2-like), and proteins with Hsp70 domains (Hsp70-like) which have been previously characterized and demonstrated to be related toT. cruzivirulence. PSPs found inT. rangeliwere related to protozoan metabolism, specifically carboxylases and phosphatases. Furthermore, we also identified PSPs that may interact with the human immune system, including heat shock and MASP proteins, but in a lower number compared toT. cruzi. Interestingly, we describe a hypothetical hybrid interactome of PSPs which reveals thatT. cruzisecreted molecules may be down-regulating IL-17 whilstT. rangelimay enhance the production of IL-15. These results will pave the way for a better understanding of the pathophysiology of Chagas disease and may ultimately lead to the identification of molecular targets, such as key PSPs, that could be used to minimize the health outcomes of Chagas disease by modulating the immune response triggered byT. cruziinfection. (AU)

Processo FAPESP: 16/15000-4 - Trypanosoma cruzi: variabilidade genômica intra- e interespecífica e mecanismos de invasão/evasão celular
Beneficiário:Renato Arruda Mortara
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 15/50315-3 - Geometry and dynamics between Ohio and São Paulo
Beneficiário:Paolo Piccione
Linha de fomento: Auxílio à Pesquisa - Regular