Review: Gp-340/DMBT1 in mucosal innate immunity

Area of Science:

• Immunology
• Molecular Biology
• Microbiology

Background:

• Deleted in Malignant Brain Tumour 1 (DMBT1) encodes multifunctional proteins involved in mucosal innate immunity.
• Two main DMBT1 isoforms, gp-340 and salivary agglutinin (SAG), are secreted in broncho-alveolar fluid and saliva, respectively.
• These isoforms are identical and play roles in host defense against pathogens.

Purpose of the Study:

• To elucidate the multifaceted roles of DMBT1 proteins in innate immunity and host defense.
• To investigate the interactions of DMBT1 isoforms with various microbial and host molecules.
• To highlight the significance of Dmbt1-deficient mice models for in vivo functional studies.

Main Methods:

• In vitro interaction assays to study binding and agglutination properties of DMBT1 isoforms.
• Analysis of DMBT1 interactions with bacteria (e.g., Streptococcus mutans), viruses (e.g., Influenza A, HIV-1), and host proteins (e.g., SP-D, IgA, C1q).
• Utilization of Dmbt1-deficient mice for in vivo functional validation.

Main Results:

• DMBT1 isoforms agglutinate Gram-negative and Gram-positive bacteria, including Streptococcus mutans.
• DMBT1(gp340) interacts with surfactant proteins A and D (SP-D), and together they agglutinate Influenza A virus.
• DMBT1(gp340) binds HIV-1, facilitating viral transcytosis, and interacts with other innate immunity and wound-healing molecules like IgA, C1q, and TFF2.

Conclusions:

• DMBT1 proteins are key components of the innate immune system with broad antimicrobial and antiviral activities.
• Their interactions with diverse host and pathogen molecules underscore their critical role in mucosal defense.
• The development of Dmbt1-deficient mice enables comprehensive in vivo investigation of DMBT1 functions.