Lysosome biogenesis/scattering increases host cell susceptibility to invasion by Trypanosoma cruzi metacyclic forms and resistance to tissue culture trypomastigotes

Autor(es)

Cortez, Cristian ^[1] ; Real, Fernando ^{[1, 2]} ; Yoshida, Nobuko ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, R Pedro de Toledo 669-6 Andar, BR-04039032 Sao Paulo, SP - Brazil

^[2] Inst Cochin, INSERM U1016, Dept Infect Immun & Inflammat, Paris - France

• Tipo de documento: Artigo Científico
• Fonte: Cellular Microbiology; v. 18, n. 5, p. 748-760, MAY 2016.
• Citações Web of Science: 11

Resumo

A fundamental question to be clarified concerning the host cell invasion by Trypanosoma cruzi is whether the insect-borne and mammalian-stage parasites use similar mechanisms for invasion. To address that question, we analysed the cell invasion capacity of metacyclic trypomastigotes (MT) and tissue culture trypomastigotes (TCT) under diverse conditions. Incubation of parasites for 1h with HeLa cells in nutrient-deprived medium, a condition that triggered lysosome biogenesis and scattering, increased MT invasion and reduced TCT entry into cells. Sucrose-induced lysosome biogenesis increased HeLa cell susceptibility to MT and resistance to TCT. Treatment of cells with rapamycin, which inhibits mammalian target of rapamycin (mTOR), induced perinuclear lysosome accumulation and reduced MT invasion while augmenting TCT invasion. Metacylic trypomastigotes, but not TCT, induced mTOR dephosphorylation and the nuclear translocation of transcription factor EB (TFEB), a mTOR-associated lysosome biogenesis regulator. Lysosome biogenesis/scattering was stimulated upon HeLa cell interaction with MT but not with TCT. Recently, internalized MT, but not TCT, were surrounded by colocalized lysosome marker LAMP2 and mTOR. The recombinant gp82 protein, the MT-specific surface molecule that mediates invasion, induced mTOR dephosphorylation, nuclear TFEB translocation and lysosome biogenesis/scattering. Taken together, our data clearly indicate that MT invasion is mainly lysosome-dependent, whereas TCT entry is predominantly lysosome-independent. (AU)

• Processo FAPESP: 11/51475-3 - Biologia molecular e celular do parasitismo por Trypanosoma cruzi
• Beneficiário: José Franco da Silveira Filho
• Modalidade de apoio: Auxílio à Pesquisa - Temático