NALP3 is not necessary for early protection against experimental tuberculosis

作者：Walter Kerstin; Hoelscher Christoph; Tschopp Juerg; Ehlers Stefan^*

来源：Immunobiology, 2010, 215(9-10): 804-811.

DOI：10.1016/j.imbio.2010.05.015

• Tuberculosis
• Innate immunity
• NOD-like receptor
• Interleukin-18
• Granuloma

In vitro, Toll-like receptors (TLR)2, 4 and 9 as well as NOD-like receptor 2 critically determine macrophage responses to Mycobacterium tuberculosis (Mtb) infection. However, in low-dose experimental murine tuberculosis, single or multiple deficiencies in TLRs 2, 4, 9 or NOD2 have little, if any, impact on early mycobacterial growth containment, granuloma formation and survival. Here, we analyzed the relevance of NALP3, one component of the danger-signaling inflammasome, for (i) Mtb-induced cytokine secretion in vitro and in vivo, (ii) restriction of Mtb replication in infected organs and (iii) granuloma formation. In the absence of functional NALP3, there was no IL-1 beta and IL-18 production in Mtb-infected dendritic cells and macrophages in vitro, whereas secretion of IL-1 alpha, IL-12p40 and TNF remained unaffected. After three weeks of infection, NALP3-deficient as well as IL-18-deficient mice were as capable as wildtype mice of restricting Mtb loads at a plateau level within well-differentiated granulomas. In conclusion, despite its involvement in cytokine processing, NALP3 is not essential for induction of protective immunity to Mtb.

• 出版日期2010-10