Modulation of host immune responses by helminth glycans

Summary: Parasitic infections regulate/alter host immune responses. Among parasitic infections, helminth infection often leads to systemic immune suppression or anergy. Helminth infection or helminth extracts drive CD4 + T‐helper (Th) cell responses towards Th2 type and activate antigen‐presenting cells (APCs) such that these cells express an anti‐inflammatory phenotype. Among the myriad molecules present on or secreted by helminth parasites, glycans have been shown to be key in inducing Th2‐type and anti‐inflammatory immune responses. The majority of studies on immune modulatory helminth glycans have focused on Lacto‐N‐fucopentaose III and Lewis X . When presented as glycol‐conjugates, with multiple copies of the sugars conjugated to a carrier molecule, these compounds activate APCs, inducing an alternative activation pattern, whose phenotypic profile is substantially different than that seen using pro‐inflammatory activators such as lipopolysaccharide. Though the mechanism of APC activation by LNFPIII/Lewis X glycoconjugates has not been fully elucidated, it involves C‐type lectin ligation on the surface of APCs, with subsequent antagonism of Toll‐like receptor signaling. In this article, we discuss the APC surface receptors known to play roles in LNFPIII/Lewis X induced alternative activation of APCs. We also discuss what is currently known regarding downstream signaling pathways, closing with a discussion of future research directions for this field of investigation including the potential use of immune modulatory glycans as vaccine adjuvants and anti‐inflammatory therapeutics.