Nod-like receptors in intestinal host defense: controlling pathogens, the microbiota, or both?

Nod-like receptors (NLRs) are intracellular innate immune sensors of microbes and danger signals that control multiple aspects of inflammatory responses. We review the evidence that highlights the critical importance of NLRs in the host response to intestinal pathogens. Moreover, we discuss the potential roles played by NLRs in the dynamic control of the intestinal microbiota and how commensal microorganisms may affect host susceptibility to enteric bacterial pathogens through interactions with NLRs as well as with invading pathogens.

Recent studies targeting the intestinal microbiota in the context of NLR deficiencies suggest inherent alterations in bacterial density or abundance may underlie the development of inflammatory diseases. As commensal microorganisms may also affect host susceptibility to enteric bacterial pathogens, NLRs might promote intestinal innate immune defense through mechanisms more complex than previously anticipated.

The inclusion of the intestinal microbiota as a critical parameter in innate immunity represents an exciting new dimension for understanding NLR functioning and the clinical implications for human health.