Asha Hassan
University of Nottingham
UK
Title: The sequestration of human dendritic cells by the infective L3 Necator americanus
Biography
Biography: Asha Hassan
Abstract
Despite the profound health implications of Necator americanus (N. americanus) infection in humans, many aspects of its interaction with the host immune system are poorly understood. In this context, we studied the direct effects of N. americanus larvae (L3) on the phenotype and function of human dendritic cells (DCs). For the first time our data show that L3 N. americanus larvae exsheathed in the presence of DCs and sequestered the immune cells onto the discarded cuticle sheath. Intriguingly, bystander DCs had negligible interaction with the emerging larvae, alluding to a disparity between the surface chemistry of the larval sheath and its cuticle. Our data also suggest that the interaction between DCs and larvae is mediated via C-type lectin receptors (CLRs) as evidenced by an inhibition in DC sequestration on the larvae cuticle after blocking DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin) or MR (mannose receptor).
Additionally, DCs incubated with viable axenic larvae exhibited an immature phenotype as evidenced by the low expression of the maturation markers CD80, CD83, CD86, CD40, andHLA-DR. However, DCs maintained their ability to acquire a mature phenotype in response to LPS. Cytokine expression by DCs stimulated with the larvae was comparable to untreated DC,with a statistical significance in contrast to LPS treated DCs (p≤0.029 IL-6, 8 and 10). DCs co-stimulated with LPS and N. americanus exhibited an overall suppression of anti- and pro-nflammatory cytokines (IL-6, IL-8, IL-10 and IL-12). Conclusively, mature DCs lyse the parasite, which is thought to be mediated through DC modification of cytokine secretions in the microenvironment via paracrine signalling to directly eliminate and lyse the pathogen.These data provide new insights into early immunological events at the interface of DCs and N. americanus larvae and could explain how L3 evade immunity upon initial interaction with ntigen presenting cells; an essential measure for disease prevention, which will be published later this year