Application of mass spectrometry-based proteomics and lipidomics to search for molecular alterations in the host infected by Leishmania spp.

Author(s)

Fernanda Negrão

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2020-01-24

Examining board members

Marcos Nogueira Eberlin; Alessandra Sussulini; Fernanda Janku Cabral; Giuseppe Palmisano; Anita Hilda Straus

• Advisor: Selma Giorgio; Marcos Nogueira Eberlin

Abstract

Leishmaniasis is a parasitic disease that presents itself in various clinical forms (cutaneous, mucocutaneous and visceral) depending on the "Leishmania" species and on the host¿s immune response. "Leishmania spp". need host cells, especially mononuclear phagocytes, to complete its life-cycle. Therefore, understanding the Leishmania-host interaction is fundamental to develop means to control the infection, such as new therapies and vaccination. However, the details about this interaction remain unclear. The present work applies mass spectrometry (MS) based imaging, proteomics and lipidomics to analyze protein and lipid alterations in the host after "L. amazonensis" and "L. major" infection, the causative agents of the cutaneous form of the disease, and, "L. infantum", the causative agent of the visceral form. The application of imaging MS was performed to observe the spatial distribution of proteins in murine cutaneous lesions induced by "L. amazonensis" or "L. major" at different infection timings. Our results demonstrated the application of imaging MS as a potential diagnostic and biomarker¿s discovery tool for cutaneous leishmaniasis. Then, MS-based proteomics was applied to identify and quantify protein alterations of infected macrophages and of murine cutaneous lesions induced by "Leishmania spp".. Lastly, MS-based lipidomics was applied to identify and quantify lipid alterations, possibly linked to the visceralization of the disease, in macrophages infected by "L. amazonensis" or "L. infantum". Therefore, through the relative quantification of proteins and lipids in the host after infection induced by "Leishmania spp"., our results revealed candidates to be further investigated as therapeutic targets or potential biomarkers that can contribute to a better understanding of the pathophysiology of leishmaniasis (AU)

• FAPESP's process: 16/11517-2 - Cutaneous leishmaniasis biomarkers candidates search and identification through mass spectrometry
• Grantee: Fernanda Negrão Silva
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)