RESUMO
Productive HIV infection of CD4(+) T cells leads to a caspase-independent cell death pathway associated with lysosomal membrane permeabilization (LMP) and cathepsin release, resulting in mitochondrial outer membrane permeabilization (MOMP). Herein, we demonstrate that HIV infection induces damage-regulated autophagy modulator (DRAM) expression in a p53-dependent manner. Knocking down the expression of DRAM and p53 genes with specific siRNAs inhibited autophagy and LMP. However, inhibition of Atg5 and Beclin genes that prevents autophagy had a minor effect on LMP and cell death. The knock down of DRAM gene inhibited cytochrome C release, MOMP and cell death. However, knocking down DRAM, we increased viral infection and production. Our study shows for the first time the involvement of DRAM in host-pathogen interactions, which may represent a mechanism of defense via the elimination of infected cells.
Assuntos
Autofagia , Linfócitos T CD4-Positivos , Infecções por HIV/metabolismo , HIV/fisiologia , Interações Hospedeiro-Patógeno/fisiologia , Membranas Intracelulares/metabolismo , Lisossomos/metabolismo , Proteínas de Membrana/biossíntese , Proteína 5 Relacionada à Autofagia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Citocromos c/genética , Citocromos c/metabolismo , Feminino , Regulação da Expressão Gênica , Infecções por HIV/genética , Humanos , Lisossomos/genética , Lisossomos/virologia , Masculino , Proteínas de Membrana/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Permeabilidade , Proteína Supressora de Tumor p53/biossínteseRESUMO
Zampieri and colleagues used sophisticated statistical methods to create a picture of acid-base pattern and inflammation relationship in a clinical context. The observed independent relationship between acidosis and albumin concentration and inflammatory pattern opens up a new area for research. It has become clear that, in addition to the characterization of mediators, receptors, and cellular phenotypes, the inflammatory response has to be interpreted in light of acid-base status, albumin concentration, and probably also carbon dioxide level.