Toll-like receptor 2: An important regulator of the Mycobacterium tuberculosis granuloma (45.23)

Abstract

Abstract Tubercle granulomas are highly organized immune structures that protect the host against Mycobacterium tuberculosis (Mtb) infection. The organization of immune cells around infected macrophages serves to sequester Mtb and enhance macrophage microbicidal responses. In addition, the granuloma localizes inflammation, thereby preventing damage to surrounding lung tissue. Although there is controversy regarding the involvement of Toll-like receptor 2 (TLR2) in host defense against Mtb, our findings indicate that TLR2 may be playing a key role in regulating these two opposing functions of the Mtb granuloma. Comparative studies between wild type and TLR2 gene-deficient mice demonstrated that the absence of TLR2 did not affect the magnitude of the Th1 effector response generated following aerosol infection with Mtb or the induction of recall Th1 memory immunity in response to Mtb challenge. However, the consequence of TLR2 absence was manifested at the level of the granuloma. Analysis of lungs from chronically-infected TLR−/− mice revealed increased bacterial burden and loss of granuloma integrity in comparison with infected WT mice. The infected lungs of TLR2−/− mice also exhibited enhanced inflammation and reduced Foxp3+ regulatory T cells. Together, these findings provide insights into how TLR2 might regulate the tubercle granuloma.