Mycobacterial Glycolipids – Role in Immunomodulation and Targets for Vaccine DevelopmentSubmit Manuscript on this topic
Diseases caused by mycobacteria are of global importance. It is estimated that about 23% of the global population is infected with Mycobacterium tuberculosis (Mtb), leading to 1.4 million deaths annually due to tuberculosis (TB) with one fifth of adult deaths occurring in poor/low-income countries. Other mycobacterial diseases such as leprosy and the disease caused by Mycobacterium ulcerans (Buruli ulcer) are also very important and mainly affect individuals in poor countries.
Owing to their high disease burden, interrupting disease transmission of mycobacterial infections is of crucial importance globally. This would not only require early detection of infected individuals combined with adequate treatment, but also prevention through vaccination. Effective tools to achieve early diagnosis for all mycobacterial infections remain mostly lacking and the only vaccine in use is BCG. For this reason, an intense research effort directed towards designing novel and better vaccination strategies and diagnostic tools is currently underway. While most of these efforts have focused on protein/peptide antigens, targeting of carbohydrates and glycolipids is emerging in recent years. In this regard, some of the most successful vaccines against bacterial infections like Streptococcus pneumoniae and Neisseria meningitidis are glycoconjugate vaccines that contain carbohydrate antigens conjugated to a carrier protein.
Glycolipids such as lipoarabinomannan (LAM), trehalose dimycolate (TDM) and phenolic glycolipids (PGL) constitute a unique and important part of the mycobacterial cell envelope and are some of the most potent mycobacterial antigens with immunomodulatory functions. LAM and its biosynthetic relatives - phosphatidylinositol mannosides (PIMs) and lipomannan (LM) act as agonists of several pattern recognition receptors including TLR2, DC-SIGN, Dectin-2 as well as antigens for CD1-restricted T cells. TDM is a highly immunostimulatory molecule that acts as a potent adjuvant via recognition by the C-type lectin Mincle. On the other hand, phenolic glycolipids of several mycobacterial species have negative immunomodulatory effects on the host innate immune response. Further efforts to uncover the roles of mycobacterial glycolipids in the pathogenesis of and immune response to mycobacterial infections are needed.
This Research Topic aims to provide a comprehensive overview of and recent advances in the role of glycolipids in modulating innate and adaptive immunity in TB and other mycobacterial diseases such as leprosy or Buruli ulcer. We welcome the submission of Original Research Articles, Reviews and Mini-Reviews that focus on understanding the structure and functions of mycobacterial glycolipids and their receptors; as well as their mechanisms of immunomodulation with the aim of utilizing them as vaccine components and/or adjuvants.