Streptococcus gordonii promotes rapid differentiation of monocytes into dendritic cells through interaction with the sialic acid-binding adhesin

Abstract

Infective endocarditis is frequently attributed to oral streptococci. Although the pathogenetic mechanisms are not well understood, interaction between streptococci and phagocytes is thought to be important for infective endocarditis. In this study, HL-60 cell-derived monocytes were characterized following interaction with Streptococcus gordonii DL1. Exposure of monocytes to S. gordonii DL1 induced up-regulation of the dendritic cell (DC) markers CD83, CD1a, CD86, and interleukin-12, while monocyte markers PU.1 and MafB, which are typically present at low levels in mature DCs, were down-regulated. Interaction of HL-60-derived monocytes with S. gordonii DL1 was instructive for DC differentiation in the absence of released cytokines. Furthermore, neither the filtered culture medium of S. gordonii nor the hsa mutant, deficient in sialic acid-binding activity, was able to induce the differentiation of HL-60 cells. Taken together, these data suggest that monocytes stimulated with S. gordonii DL1 rapidly undergo monocyte-to-DC differentiation through interaction with the bacterial surface receptor Hsa and that this response may be the initial step in infective endocarditis by oral streptococci.

Two Arginine Residues of Streptococcus gordonii Sialic Acid-Binding Adhesin Hsa Are Essential for Interaction to Host Cell Receptors

“…S . gordonii adhere to saliva-coated hydroxyapatite, an experimental model of the tooth surface, and bind to host cells such as erythrocytes, platelets, polymorphonuclear leukocytes (PMNs), macrophages, and monocytes [ 5 – 10 ]. A common mechanism for these interactions is the recognition of surface-associated host sialoglycoconjugates.…”

The Sialic Acid Binding Protein, Hsa, in Streptococcus gordonii DL1 also Mediates Intergeneric Coaggregation with Veillonella Species

“…gordonii to human cells including heart tissues [ 31 ]. Thus, Hsa has been considered an important virulence factor in infective endocarditis [ 32 , 33 ]. Our finding demonstrates, for the first time, that Hsa is perhaps a multivalent adhesin mediating not only attachment to mammalian cells but also to prokaryotic cells.…”

Contribution of <i>Streptococcus gordonii</i> Hsa Adhesin to Biofilm Formation

“…In addition, Hsa adhesin contributes to the pathogenesis of experimental infectious endocarditis caused by S. gordonii DL1 (6). Moreover, the results of our recent study suggested that monocytes stimulated with S. gordonii DL1 rapidly differentiate into dendritic cells through interactions with Hsa (19).…”

“…The Hsa adhesin and its homologs facilitate attachment of S. gordonii to host cells, such as polymorphonuclear leukocytes (13,16), erythrocytes (7,15), platelets (9,14,17,18), macrophages, and monocytes (19). In addition, Hsa adhesin contributes to the pathogenesis of experimental infectious endocarditis caused by S. gordonii DL1 (6).…”