Researchers found that the mycobacterial sugar molecule, α-glucan, binds to dectin-1 on host macrophages, which promotes the pathogen’s survival.
Successful infection often depends on a pathogen’s ability to evade host immune cell detection through stealthy mechanisms. After a person inhales Mycobacterium tuberculosis (MTB) into their lungs, phagocytic cells such as macrophages engulf it. Although innate pattern recognition receptors (PRRs) on macrophages recognize the bacteria and activate intracellular immune responses, MTB can dodge these defenses to survive and facilitate the development of tuberculosis.
The PRR dectin-1 recognizes β-glucan sugars on the surface of fungal pathogens. While dectin-1 is best known for playing a role in protective antifungal immunity, accumulating evidence also suggests that it contributes to immune responses against other pathogens, such as mycobacteria, although the underlying mechanisms remain incompletely understood.1
This motivated Shota Torigoe, a bacteriologist at the Japan Institute for Health Security, to investigate dectin-1’s function in the context of MTB infections. In a recent study, published in Science Immunology, Torigoe and his colleagues found that a dectin-1 deficiency in mice increased their resistance to MTB infection.2 In addition, the team found that mycobacterial α-glucans can bind to dectin-1; if the mycobacteria lacked this sugar, it had poorer survival rates within mice and human macrophages. Thus, these findings demonstrate that dectin-1–α-glucan interactions promote intracellular bacterial survival.
The researchers first examined the function of dectin-1 during MTB infection in wild type mice and mice genetically deficient in dectin-1. Mice with macrophages lacking dectin-1 exhibited increased resistance to MTB infection, a reduced inflammatory response, and lived longer than their counterparts. Based on these findings, the researchers hypothesized that dectin-1 influenced innate immune responses during infection.
To further explore this, the team conducted in vitro experiments focusing on macrophages, which play a central role in tuberculosis pathogenesis. When macrophages gobbled up MTB, higher levels of dectin-1 expression were associated with increased bacterial burden. Rather than being efficiently degraded within phagosomes, MTB persisted. The researchers found that elevated dectin-1 expression disrupted phagosome maturation and suppressed antibacterial autophagy pathways. By modulating these immune processes, mycobacteria were able to enhance their intracellular survival.
Given that mycobacteria do not express β-glucans, the researchers sought to identify the mycobacterial ligand recognized by dectin-1. Through a series of purification and characterization experiments, they discovered that both mouse and human dectin-1 bind to α-glucan. Further experiments showed that mycobacteria lacking α-glucan had significantly reduced survival within both mouse and human macrophages.
Although dectin-1 is traditionally associated with protective immune responses against fungal infections, these findings reveal that its presence can instead facilitate mycobacterial survival. This study highlights one of MTB’s survival mechanisms and advances understanding of host–pathogen interactions during tuberculosis infection. While additional research is needed, these insights may inform future therapeutic strategies targeting this pathway.
