A Role for Human SPα as a Pattern Recognition Receptor

Abstract Human Spα is a soluble protein belonging to group B of the scavenger receptor cysteine-rich (SRCR) superfamily for which little functional information is available. It is expressed by macrophages present in lymphoid tissues (spleen, lymph node, thymus, and bone marrow), and it binds to myelomonocytic and lymphoid cells, which suggests that it may play an important role in the regulation of the innate and adaptive immune systems. In the present study we show that recombinant human Spα (rSpα) binds to the surface of several Gram-positive and Gram-negative bacterial strains. Competition studies indicated that such binding is mediated by the recognition of lipoteichoic acid (LTA) and lipopolysaccharide (LPS), respectively, through nonoverlapping sites on the Spα molecule. The most conserved part of LPS (2-keto-3-deoxyoctulosonic acid and lipid A) was shown to be involved in the recognition by Spα. Bacterial binding studies using the SRCR domain 1 of Spα showed that this domain retains both the LPS and LTA binding activities, indicating that both bacterial interacting sites are retained in a single SRCR domain. Furthermore, rSpα induced aggregation of Gram-positive and Gram-negative bacteria strains. On the other hand, rSpα inhibited tumor necrosis factor-α secretion by human monocytes stimulated with LPS or LTA. Binding of Spα to conserved components of bacterial surfaces and modulation of the monocyte response indicate that this molecule is an active constituent of the innate immune response of the host.