Recognition of Mycobacterial Lipids by Immune Receptors

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), infects one-third of the world's population and causes 1.5 million deaths each year. The cell envelopes of mycobacteria comprise a wealth of unique glycolipids, including trehalose-6,6'-dimycolate (TDM), lipoarabinomannan (LAM), lipomannan (LM), and phosphatidylinositol (PI) mannosides (PIMs). These lipids are important modulators of the host immune responses during infection and in some cases have been used as adjuvants [e.g., complete Freund's adjuvant (CFA)]. Despite this abundant basic knowledge, the identities of the host immune receptors for mycobacterial lipids have long been elusive. Here we review and summarize our current state of knowledge regarding innate immune receptors for mycobacteria, focusing particularly on immunoreceptor tyrosine-based activation motif (ITAM)-coupled C-type lectin receptors (CLRs), which have been shown to recognize mycobacteria-derived glycolipids.