Banca de QUALIFICAÇÃO: VIVIANE BRITO NOGUEIRA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : VIVIANE BRITO NOGUEIRA
DATE: 30/09/2022
TIME: 09:30
LOCAL: REMOTA - https://meet.google.com/scs-stcf-izh
TITLE:

IMPAIRED MEMBRANE TRAFFICKING ON BERARDINELLI-SEIP CONGENITAL LIPODYSTROPHY MACROPHAGES DURING LEISHMANIA INFANTUM INFECTION

KEY WORDS:

Congenital generalized lipodystrophy; Macrophages; Amastin; AGPAT2; BSCL2; Seipin

PAGES: 32
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Berardinelli-Seip Congenital Lipodystrophy (CGL) is an autosomal recessive disorder characterized by nearly complete lack of adipose tissue, metabolic syndrome and hypoleptinemia. CGL patients usually have premature death caused by liver and cardiovascular diseases or infections. Here, we evaluate the impaired lipid metabolism influence on the CGL cells’ prior and after infection with Leishmania infantum. Dual RNA-seq of human monocyte-derived macrophages (MD-Mø) from Type 1 (AGPAT2mut) and Type 2 (BSCL2mut), heterozygous for Type 2 (BSCL2het), and Wild Type (WT) were performed. The infected MD-Mø of individuals with CGL either AGPAT2 or BSCL2 showed differences in gene expression with signature for membrane trafficking pathways. AGPAT2mut and BSCL2mut groups had in common a downregulation of endocytic-related pathways and immunological synapse. However, exclusively, AGPAT2mut cells showed a difference in collagen metabolism and BSCL2mut cells in lipid rafts. L. infantum gene expression was also altered in relation to the interaction with membranes: amastin (a surface glycoprotein that operates at the host-parasite interface) was downregulated in CGL, whereas Leishmania GP63 (a virulence factor that uses lipid rafts for cell entry) and AAT19 (a surface amino acid transporter) were upregulated in CGL cells. For BSCL2het individuals, despite the minimal difference in gene expression in non-infected cells, there was a substantial increase in host gene expression modulation in response to L. infantum infection. The genes were functionally similar to homozygous individuals e.g. immunological synapse and plasma membrane pathways, but no differences for the L. infantum gene expression was found. Overall, this work reveals that the CGL cells have a discernible transcriptomic signature associated with membrane trafficking impairment when responding to L. infantum infection, more likely due to altered lipid metabolism; and that in vitro infection of CGL cells can be model approach to study lipid metabolism and its relationship with infectious processes.

COMMITTEE MEMBERS:
Presidente - 350647 - SELMA MARIA BEZERRA JERONIMO
Externa ao Programa - 1714243 - DANIELLA REGINA ARANTES MARTINS SALHA - UFRNExterno ao Programa - 1513597 - JOAO PAULO MATOS SANTOS LIMA - UFRN