Escherichia coli K1 Induces the Upregulation of CD47 in Myeloid Dendritic Cells

Abstract

Escherichia coli K1 is one of the most common pathogens that cause meningitis in neonates. Studies have shown that a high degree of bactremia is required for E. coli K1 to cross the blood‐brain barrier, indicating that the bacterium must evade host immune defense mechanisms and survive in the blood. Dendritic cells (DCs) are the most potent antigen presenting cells that play a crucial role in initiation and modulation of specific immune responses. Nonetheless, very little is known about the interaction of E. coli K1 with DCs. Here, our studies demonstrated that the interaction of OmpA+ E. coli K1 with DCs enhances the expression of CD47, an integrin associated molecule reported to induce tolerogenicity in immune cells like T cells. Significant increase in the expression of TSP‐1, a natural ligand for CD47, on the surface of DCs was also observed. In contrast, OmpA− E. coli, which promotes the maturation of DCs, failed to upregulate the expression of CD47 and TSP‐1 in DCs. Pretreatment of DCs with CD47 blocking antibodies led to maturation of DCs substantiating the role of CD47 in OmpA+ E. coli K1 mediated tolerogenicity. Furthermore, OmpA+ E. coli K1 infected DCs failed to present antigen to T cells. The present study identified an important and novel mechanism by which E. coli K1 makes DCs tolerogenic by upregulating the expression of CD47. Targeting CD47 might help in restoring maturation of DCs in response to E. coli K1 leading to efficient antigen presentation thus promoting clearance of bacteria.