L-Rhamnose is a non-mammalian monosaccharide ubiquitously found on the surface of both commensal and pathogenic bacteria. Previous publications had identified that L-rhamnose-rich Mycobacterium tuberculosis glycolipids, and their structural derivatives, pHBADs, were able to aid this pathogen's ability to escape immune elimination by repressing protective immune responses. A key immune cell for combatting M. tuberculosis is the macrophage, an innate immune cell present in essentially all tissues. A distinguishing feature of macrophages is their polarisation combined with plasticity; the ability to adopt distinct phenotypes. These are simplified into the pro-inflammatory and bactericidal, "classically activated" M1 macrophages and the "alternatively activated" Th2-promoting and anti-inflammatory M2 macrophages. To combat M. tuberculosis, M1 macrophage activation is critical. In the research presented herein, it is demonstrated that L-rhamnose skews macrophage polarisation away from a bactericidal phenotype and enhances M2 characteristics. Furthermore, it is revealed that L-rhamnose is capable of inducing macrophage innate memory, causing responses elicited by subsequent stimuli, a week after L-rhamnose incubation, to yield a more anti-inflammatory and anti-bactericidal profile. Moreover, by investigating synthetic pHBAD analogues it was confirmed that L-rhamnose confers immunomodulatory properties to these molecules. Summarily, it appears that L-rhamnose confers M. tuberculosis with immunomodulatory properties that protects it from macrophage bactericidal responses.

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