Dectin-1-Mediated DC-SIGN Recruitment to Candida albicans Contact Sites

At host–pathogen contact sites with Candida albicans, Dectin-1 activates pro-inflammatory signaling, while DC-SIGN promotes adhesion to the fungal surface. We observed that and collaborate enhance capture/retention of C. albicans under fluid shear culture conditions. Therefore, we devised a cellular model system wherein could investigate interaction between these two receptors during earliest stages interaction. In cells expressing both receptors, was quickly recruited (103.15% increase) but did not similarly accumulate. Once inside site, FRAP studies revealed strong reduction in lateral mobility (but Dectin-1), consistent engaging multivalent adhesive binding interactions cell wall mannoprotein ligands. Interestingly, absence co-expression, recruitment much poorer—only 35.04%. These data suggested active site. proposed signaling RHOA pathway, leading actomyosin contractility recruitment, perhaps via formation centripetal flow (AMF) directed into Indeed, pathway inhibitors significantly reduced Dectin-1-associated used agent-based modeling predict transport kinetics (“Directed + Brownian”) without (“Brownian”) hypothesized flow-mediated transport. The Directed Brownian predicted site (106.64%), similar experimentally receptor co-expression. diffusive alone only 55.60%. However, this value or treated inhibitor, suggesting it accurately when AMF would be generated. TIRF microscopy nascent contacts on glucan-coated glass Dectin-1-dependent F-actin (LifeAct) early stage membranes. entry followed temporal lag 8.35 ± 4.57 s, correlation disrupted by treatment inhibitor. Thus, computational experimental evidence provides support for existence Dectin-1/RHOA-dependent produces force drive pathogen sites, resulting improved capture retention immunocytes. suggest rapid collaborative response sties might important efficient acquisition yeast conditions, such as those prevail circulation mucocutaneous infection.