Toll-like receptor 9 participation in experimental Th type 1 (Mycobacterial) pulmonary granuloma formation (44.15)

Abstract

Abstract We have established that experimental Th type 1 (Th1) responses can be studied in mice by sensitizing with Mycobacterium bovis purified protein derivative (PPD) followed by an intravenous challenge of agarose beads covalently coupled to the respective sensitizing Ags. Mycobacterial antigens (Ags) stimulate antigen presenting cells (APCs) through distinct Toll-like receptors (TLRs) resulting in rapid activation of the innate immune system. Toll-like receptor 9 (TLR9) is known to play an important role in the regulation of Th1 responses. The role of TLR9 during infection with Mycobacterium Ags has been under investigated. We demonstrate in this study that TLR9−/− mice showed greatly increased granuloma formation as assessed by morphometric analysis, and an increase in eosinophil and stromal cells, suggesting a Th-2 skewing, as compared with wild-type. Moreover, Th1 cytokine production of IL-12 and IFN-gamma was abrogated in TLR9−/− mice. These results suggest that TLR9 plays an important role in maintaining a Th1-type pulmonary granulomatous response. This work was supported by NIH grants HL031963, HL074024, and HL031237.