Mycobacterium tuberculosis Requires Cholesterol Oxidase to Disrupt TLR2 Signalling in Human Macrophages

Cholesterol Oxidase Binds TLR2 and Modulates Functional Responses of Human Macrophages

Cholesterol oxidase (ChoD) is considered to be an important virulence factor for Mycobacterium tuberculosis (Mtb), but its influence on macrophage activity is unknown. Here we used Nocardia erythropolis ChoD, which is very similar to the Mtb enzyme (70% identity at the amino-acid level), to evaluate the impact of bacterial ChoD on the activity of THP-1-derived macrophages in vitro. We found tha...

Cholesterol Oxidase Is Indispensable in the Pathogenesis of Mycobacterium tuberculosis

Despite considerable research effort, the molecular mechanisms of Mycobacterium tuberculosis (Mtb) virulence remain unclear. Cholesterol oxidase (ChoD), an extracellular enzyme capable of converting cholesterol to its 3-keto-4-ene derivative, cholestenone, has been proposed to play a role in the virulence of Mtb. Here, we verified the hypothesis that ChoD is capable of modifying the bactericida...

PE_PGRS33 Contributes to Mycobacterium tuberculosis Entry in Macrophages through Interaction with TLR2

PE_PGRS represent a large family of proteins typical of pathogenic mycobacteria whose members are characterized by an N-terminal PE domain followed by a large Gly-Ala repeat-rich C-terminal domain. Despite the abundance of PE_PGRS-coding genes in the Mycobacterium tuberculosis (Mtb) genome their role and function in the biology and pathogenesis still remains elusive. In this study, we generated...

Mycobacterium tuberculosis replicates within necrotic human macrophages

Mycobacterium tuberculosis modulation of macrophage cell death is a well-documented phenomenon, but its role during bacterial replication is less characterized. In this study, we investigate the impact of plasma membrane (PM) integrity on bacterial replication in different functional populations of human primary macrophages. We discovered that IFN-γ enhanced bacterial replication in macrophage ...

Macrophages Requires Phospholipase D Within Human Mycobacterium tuberculosis ATP-Induced Killing of Virulent