Modulation of host immune responses by helminth glycans.
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 LewisX. 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/LewisX 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/LewisX 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.
Harn
Donald A
DA
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA. dharn@uga.edu
McDonald
Jasmine
J
Atochina
Olga
O
Da'dara
Akram A
AA
D000606:Amino Sugars / Q000276:immunology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000469:parasitology; D000947:Antigens, Helminth / Q000276:immunology*; D006376:Helminths / Q000276:immunology*; D006801:Humans; D016256:Lewis X Antigen / Q000276:immunology; D051379:Mice; D011134:Polysaccharides / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D051197:Toll-Like Receptor 4 / Q000276:immunology
D000606:Amino Sugars; D000947:Antigens, Helminth; D016256:Lewis X Antigen; D011134:Polysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C434666:lacto-N-fucopentaose III