The binding of mycolic acids to galectin‐3: A novel interaction between a host soluble lectin and trafficking mycobacterial lipids?

TLDR

Host‑pathogen interaction mechanisms, particularly the composition of mycolic acids in Mycobacterium tuberculosis that influence strain virulence, remain incompletely understood, especially regarding endogenous receptors on susceptible cells. We demonstrate that galectin‑3 binds mycolic acids, with these lipids inhibiting lectin self‑association yet preserving carbohydrate binding and selectively disrupting galectin‑3’s interaction with dendritic‑cell receptors, implicating galectin‑3 in recognizing trafficking mycolic acids during infection.

Abstract

Understanding the molecular mechanism of host‐pathogen interactions is the basis for drug design and vaccine development. The fine composition of mycolic acids (MA), the major constituents of Mycobacterium tuberculosis (Mtb) cell envelope, as well as other cell wall‐associated lipids, contribute to determine the virulence of a given strain. However, endogenous receptors for mycolic acids on susceptible cells exposed to mycobacterial infections have not been fully identified. Here, we show that galectin‐3, a multifunctional β‐galactoside binding lectin present mainly in the cytoplasm of inflammatory cells and also present on the cell surface, can recognize mycobacterial mycolic acids. MA can inhibit the lectin self‐association but not its carbohydrate‐binding abilities and can selectively interfere in the interaction of the lectin with its receptors on temperature‐sensitive dendritic cell line, suggesting that galectin‐3 could be involved in the recognition of trafficking mycolic acids and participate in their interaction with host cells.