The Role of Nod1/Nod2 in Host Defense against Microbial Infection

Abstract

The cytosolic sensors Nod1 and Nod2 and the Toll-like receptors (TLRs) activate defense signaling pathways in response to microbial stimuli. However, the role of Nod1 and Nod2 and their interplay with TLRs during bacterial infection remain poorly understood. Here, we report that bone marrow-derived macrophages made insensitive to TLRs by previous exposure to microbial ligands remained responsive to Nod1 and Nod2 stimulation. In vivo, bacterial clearance upon systemic infection with L. monocytogenes was critically dependent on Nod1 and Nod2 when mice were previously exposed to TLR ligands such as lipopolysaccharide. Furthermore, we found a critical role for Nod2 in host defense in the intestine where macrophages are known to be tolerant to TLR stimulation. Thus, Nod1 and Nod2 are important for microbial recognition and host defense under conditions in which TLR signaling is reduced.