Human innate immune cells that engage soluble beta-1,3/1,6 glucans: Role for complement receptor 3 (CR3, CD11b/CD18) (89.53)

Abstract

Abstract Beta-1,3/1,6 glucans (BGs) are a diverse class of PAMPs. Structurally, BGs can vary on the basis of chain length, types of linkages, branching, and tertiary structure. BGs have been reported to activate various types of innate immune cells; most studies demonstrate the use of particulate BGs activating murine immune cells. Unlike particulate BGs, most soluble BGs demonstrated minimal activities typically associated with innate immune cell activation, such as induction of cytokines. Hence, little is known regarding the types of human immune cells or receptors that engage soluble BGs, and if structurally distinct BGs differ in their cell selectivity or receptor requirements. The objective of this study was to determine the types of human immune cells that soluble BGs bind to, and to determine the receptors required for binding. Since BGs have been implicated in interacting with Dectin-1 and CR3 expressing cells, we hypothesize that human innate immune cells that express these receptors will bind soluble BGs. Specific binding of BGs was evaluated by flow cytometry on primary human immune cells and cell lines using BG specific antibody and DTAF-labeled BGs. In addition, these studies were conducted using three structurally distinct, purified, and chemically characterized BGs. Key findings demonstrate that on cells that express both CR3 and Dectin-1, CR3 is a critical receptor for binding soluble BGs and not all BGs bind equivalently to human innate immune cells.