An immunomodulatory role for the Mycobacterium tuberculosis Acr protein in the formation of the tuberculous granuloma.

Abstract

The tuberculous granuloma is a compact aggregate of dormant bacteria encapsulated by host macrophages. It is commonly regarded as a product of the host defense designed to isolate infectious mycobacteria. This work demonstrates that exposure of macrophages to the Mtb heat-shock protein Acr leads to overproduction of the chemokine CXCL16, allowing the mycobacterium to exploit the innate immune response. This induction of chemokine expression is hypothesized to occur through activation of ADAM proteases, providing an immunomodulatory role for Mtb Acr in the formation of the granuloma.