Label-Free Proteomic Analysis Reveals Parasite-Specific Protein Alterations in Macrophages Following Leishmania amazonensis, Leishmania major, or Leishmania infantum Infection

Autor(es)

Negrao, Fernanda ^{[1, 2, 3]} ; Fernandez-Costa, Carolina ^[2] ; Zorgi, Nahiara ^[1] ; Giorgio, Selma ^[1] ; Eberlin, Marcos Nogueira ^[3] ; Yates, III, John R.

Afiliação do(s) autor(es)

^[1] Inst Biol, Dept Anim Biol, Rua Monteiro Lobato 255, BR-13083862 Campinas, SP - Brazil

^[2] III, Scripps Res Inst, Dept Chem Physiol, 10550 North Torrey Pines Rd, SR302, La Jolla, CA 92037 - USA

^[3] Univ Estadual Campinas, Inst Chem, Dept Organ Chem, Rua Josue de Castro SN, Room A111, BR-13083862 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ACS INFECTIOUS DISEASES; v. 5, n. 6, p. 851-862, JUN 2019.
• Citações Web of Science: 2

Resumo

Leishmania is an obligate intracellular parasite known to modulate the host cell to survive and proliferate. However, the complexity of host-parasite interactions remains unclear. Also, the outcome of the disease has been recognized to be species-specific and dependent on the host's immune responses. Proteomics has emerged as a powerful tool to investigate the host-pathogen interface, allowing us to deepen our knowledge about infectious diseases. Quantification of the relative amount of proteins in a sample can be achieved using label-free proteomics, and for the first time, we have used it to quantify Leishmania-specific protein alterations in macrophages. Protein extracts were obtained and digested, and peptides were identified and quantified using nano-LC coupled with tandem mass spectrometry analyses. Protein expression was validated by Western blot analysis. Integrated Proteomics Pipeline was used for peptide/protein identification and for quantification and data processing. Ingenuity Pathway Analysis was used for network analysis. In this work, we investigated how this intracellular parasite modulates protein expression on a host macrophage by comparing three different Leishmania species-L. amazonensis, one of the causative agents of cutaneous disease in the Amazon region; L. major, another causative agent of cutaneous leishmaniasis in Africa, the Middle East, China, and India; L. infantum, the causative agent of visceral leishmaniasis affecting humans and dogs in Latin America-and lipopolysaccharide stimulated macrophages as an in vitro inflammation model. Our results revealed that Leishmania infection downregulates apoptosis pathways while upregulating the activation of phagocytes/ leukocytes and lipid accumulation. (AU)

• Processo FAPESP: 15/23767-0 - Pesquisa de biomarcadores e desenvolvimento de linhagens de Leishmania infantum
• Beneficiário: Selma Giorgio
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/22651-4 - Investigação da relação patógeno-hospedeiro in vitro e in vivo de leishmaniose através de proteômica shotgun
• Beneficiário: Fernanda Negrão Silva
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto