Mycobacterial interaction with innate receptors: TLRs, C-type lectins, and NLRs

Abstract

The recent discovery of novel classes of receptors, including toll-like receptors and nucleotide-binding oligomerization domain (NOD)-like receptors is challenging the crucial role of the innate immune system in the recognition of Mycobacterium tuberculosis. The present review is to focus on the roles and mechanisms of specific pattern-recognition receptor-microbial interaction for the host defense against mycobacterial infections. Toll-like receptors, key players in innate immunity, are now known to be important for the initiation and coordination of host responses to Mycobacterium tuberculosis. The interaction of Mycobacterium tuberculosis with toll-like receptors triggers intracellular signaling cascades that culminate in a proinflammatory response, but can also trigger signals that dampen the innate immune response. Other membrane-bound pattern-recognition receptors, including the mannose receptor, DC-SIGN, and Dectin-1, contribute to the propagation of Mycobacterium tuberculosis inflammatory signals, and Nod-like receptors (cytosolic pattern-recognition receptors) also act in modulating host recognition of Mycobacterium tuberculosis. Interactions between toll-like receptors and other pattern-recognition receptors are also evident in responses to Mycobacterium tuberculosis, as are possible mechanisms for coordination of innate and adaptive immunity. The complexity of Mycobacterium tuberculosis-pattern-recognition receptor interactions and their effects on host cell responses suggest key roles for innate immunity in controlling Mycobacterium tuberculosis, and the possibility of developing novel therapeutics for tuberculosis that target Mycobacterium tuberculosis-regulated innate immunity pathways.