Tandem Mass Tag Proteomic Analysis of in Vitro and in Vivo Models of Cutaneous Leishmaniasis Reveals Parasite-Specific and Nonspecific Modulation of Proteins in the Host

Autor(es)

Negrao, Fernanda ; Diedrich, Jolene K. ; Giorgio, Selma ; Eberlin, Marcos N. ; Yates, John R., III

• Tipo de documento: Artigo Científico
• Fonte: ACS INFECTIOUS DISEASES; v. 5, n. 12, p. 23-pg., 2019-12-01.

Resumo

Cutaneous leishmaniasis, the most common form of leishmaniasis, is endemic in several regions of the world, and if not treated properly, it can cause disfiguring scars on the skin. Leishmania spp. infection causes an inflammatory response in its host, and it modulates the host metabolism differently depending on the Leishmania species. Since Leishmania spp. has begun to develop resistance against current therapies, we believe efforts to identify new possibilities for treatment are critical for future control of the disease. Proteomics approaches such as isobaric labeling yield accurate relative quantification of protein abundances and, when combined with chemometrics/statistical analysis, provide robust information about protein modulation across biological conditions. Using a mass spectrometry-based proteomics approach and tandem mass tag labeling, we have investigated protein modulation in murine macrophages (in vitro model) and skin biopsies after exposure to Leishmania spp. (in vivo murine model). Infections induced by L. amazonensis (endemic in the New World) and L. major (endemic in the Old World) were compared to an inflammation model to search for Leishmania-specific and nonspecific protein modulation in the host. After protein extracts obtained from in vitro and in vivo experiments were digested, the resulting peptides were labeled with isobaric tags and analyzed by liquid chromatography-MS (LC-MS). Several proteins that were found to be changed upon infection with Leishmania spp. provide interesting candidates for further investigation into disease mechanism and development of possible immunotherapies. (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