Review: Gp-340/DMBT1 in mucosal innate immunity

Abstract

Deleted in Malignant Brain Tumour 1 (DMBT1) is a gene that encodes alternatively spliced proteins involved in mucosal innate immunity. It also encodes a glycoprotein with a molecular mass of 340 kDa, and is referred to as gp-340 (DMBT1(gp340)) and salivary agglutinin (DMBT1(SAG)). DMBT1(gp340) is secreted into broncho-alveolar surface lining fluid whereas DMBT(SAG) is present in the saliva. The two molecules were shown to be identical and both interact with and agglutinate several Gram-negative and Gram-positive bacteria including Streptococcus mutans, a bacterium responsible for caries in the oral cavity. DMBT1(gp340) interacts with surfactant proteins A and D (SP-D). DMBT1(gp340) and SP-D can individually and together interact and agglutinate influenza A virus. DMBT1(gp340) also binds to HIV-1 and facilitates transcytosis of the virus into epithelial cells. DMBT1 binds to a variety of other host proteins, including serum and secretory IgA, C1q, lactoferrin, MUC5B and trefoil factor 2 (TFF2), all molecules with involvement in innate immunity and/or wound-healing processes. Recent generation of Dmbt1-deficient mice has provided the research field of DMBT1 with a model that allows research to progress from in vitro studies to in vivo functional studies of the multifunctional proteins encoded by the DMBT1 gene.

Molecular and Functional Characterization of Mouse S5D-SRCRB: A New Group B Member of the Scavenger Receptor Cysteine-Rich Superfamily

“…Archetypical members of the SRCR-SF (e.g., DMBT1/gp340/ SAG) were reported to interact with exogenous pathogens, as well as with endogenous host components (27). Therefore, it was tested whether this could also be the case for S5D-SRCRB.…”

Structural and Functional Analysis of Cell Wall-anchored Polypeptide Adhesin BspA in Streptococcus agalactiae

“…A primary host factor recognized by members of the AgI/II polypeptide family in oral streptococci and GAS is gp340, a mucin-like glycoprotein associated with the surface of mucosal tissues (17). When gp340 becomes adsorbed onto a surface, exposed cryptitopes can provide receptors for microbial adherence.…”

“…A common receptor for AgI/II polypeptides is glycoprotein-340 (gp340), an innate immunity scavenger receptor produced at mucosal surfaces (17). Fluid-phase gp340, in saliva and other mucosal secretions, agglutinates microbes for clearance from the body, whereas solid-phase gp340 adsorbed onto host surfaces provides a substratum for microbial adherence (18).…”

Deleted in malignant brain tumor 1 is secreted in the oviduct and involved in the mechanism of fertilization in equine and porcine species

“…It was then proposed as a candidate tumor suppressor gene for lung and gastrointestinal tumors caused by homozygous deletions or by a lack of expression (Mori et al 1999, Wu et al 1999, Mollenhauer et al 2000. DMBT1 is involved in epithelial differentiation and mucosal innate immunity by binding to a large panel of pathogens including HIV (Mollenhauer et al 2000, Ligtenberg et al 2010, Madsen et al 2010, Al-Awqati 2011.…”