Abstract
Sepsis is a life-threatening clinical syndrome that results from an overwhelming immune response to infection. During sepsis, immune cells are activated by sensing pathogen-associated molecular patterns and damage-associated molecular patterns (DAMPs) through pattern recognizing receptors (PRRs). Regulation of the immune response is essential to preventing or managing sepsis. Sialic acid-binding immunoglobulin-type lectin-G (Siglec-G), a CD33 group of Siglec expressed in B-1a cells and other hematopoietic cells, plays an important immunoregulatory role. B-1a cells, a subtype of B lymphocytes, spontaneously produce natural IgM which confers protection against infection. B-1a cells also produce IL-10, GM-CSF, and IL-35 to control inflammation. Sialic acids are present on cell membranes, receptors, and glycoproteins. Siglec-G binds to the sialic acid residues on the B cell receptor (BCR) and controls BCR-mediated signal transduction, thereby maintaining homeostasis of Ca++ influx and NFATc1 expression. Siglec-G inhibits NF-κB activation in B-1a cells and regulates B-1a cell proliferation. In myeloid cells, Siglec-G inhibits DAMP-mediated inflammation by forming a ternary complex with DAMP and CD24. Thus, preserving Siglec-G’s function could be a novel therapeutic approach in sepsis. Here, we review the immunoregulatory functions of Siglec-G in B-1a cells and myeloid cells in sepsis. A clear understanding of Siglec-G is important to developing novel therapeutics in treating sepsis.
Highlights
Inflammation refers to the body’s immune response to foreign particles
Sialidase treated recombinant human CD24 when combined with recombinant human Siglec-10 did not interact with each other, confirming the importance of sialic acid on CD24 for binding to Siglec-10 to transduce the downstream immunoregulatory signal, controlling damageassociated molecular patterns (DAMPs)-mediated inflammation (20)
By comparing the findings of two contradictory studies with Siglec-G-deficient mice in sepsis, we found Li et al showed that Siglec-G deficiency ameliorates hyperinflammation and immune collapse in endotoxemia (13), on the other hand, Chen’s study revealed that Siglec-G-/- mice showed detrimental outcomes in CLP-induced sepsis (20)
Summary
Inflammation refers to the body’s immune response to foreign particles. Sepsis is characterized as life threatening organ dysfunction caused by a dysregulated host response to infection (1). We discuss the role of Siglec-G in B-1a cells and other cells to regulate BCR- and PRR-mediated pathways to control inflammation in sepsis. Sialidase treated recombinant human CD24 when combined with recombinant human Siglec-10 did not interact with each other, confirming the importance of sialic acid on CD24 for binding to Siglec-10 to transduce the downstream immunoregulatory signal, controlling DAMP-mediated inflammation (20).
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