Mycobacterium tuberculosis infection and tissue factor expression in macrophages

Area of Science:

• Immunology
• Microbiology
• Pathogenesis

Background:

• Tuberculosis (TB) patients exhibit thrombotic complications, linked to aberrant tissue factor (TF) expression.
• TF, the coagulation cascade's primary activator, is implicated in thrombotic disorders and inflammation.
• Monocyte/macrophage TF expression contributes to local and systemic inflammatory responses.

Purpose of the Study:

• To investigate if Mycobacterium tuberculosis (Mtb) infection induces TF expression in macrophages.
• To identify host and pathogenic factors responsible for Mtb-induced TF expression.
• To elucidate the signaling pathways involved in Mtb-mediated TF induction.

Main Methods:

• Macrophages were treated with live virulent Mtb, gamma-irradiated Mtb (γ-Mtb), and Mtb components.
• TF activity and expression were measured, focusing on CD14(+) macrophages.
• TF transcriptional activation and signaling pathways (including TLRs) were analyzed.

Main Results:

• Both live and γ-Mtb significantly increased TF activity in macrophages, primarily CD14(+) cells.
• Mtb-induced TF expression resulted from transcriptional activation, dependent on CD14/TLR2/TLR4 cooperation.
• Mtb cell wall components mycolyl arabinogalactan peptidoglycan (mAGP), phosphatidylinositol mannoside-6 (PIM6), and lipomannan (LM) induced TF in a dose-dependent manner (mAGP>PIM6>LM). Direct bacterial-macrophage contact was crucial.

Conclusions:

• Mtb infection induces TF expression in macrophages via transcriptional activation.
• Mtb-mediated TF induction involves multiple receptors, co-receptors/co-factors, including Toll-like receptors.
• TF plays a role in granuloma formation and Mtb containment, influencing TB pathogenesis.