TREM2 receptor identified as inhibitor of immune response to Cryptococcus neoformans infection
Researchers have identified TREM2, a receptor expressed on myeloid immune cells, as a direct sensor of the fungal pathogen Cryptococcus neoformans that paradoxically suppresses the immune response. TREM2 signals through the adapter protein DAP12 to inhibit macrophage activation and fungal uptake, with the fungal cell wall component β-1,6-glucan mediating the binding interaction. This finding reveals a potential immune evasion mechanism exploited by C. neoformans and highlights the TREM2-DAP12 pathway as a possible therapeutic target for improving outcomes in cryptococcal infections.
A new preprint study published on bioRxiv reports that TREM2, a triggering receptor expressed on myeloid cells, is upregulated on murine monocytes and interstitial macrophages in the lungs during Cryptococcus neoformans infection and acts as an inhibitory regulator of the antifungal immune response. The researchers found that TREM2 signals through the adapter protein DAP12—previously shown by the same group to worsen mouse survival during cryptococcosis—to suppress both phagocytosis of fungal cells and M1 macrophage polarization, a pro-inflammatory state important for pathogen clearance. Using in vitro binding assays, the team demonstrated that both murine and human TREM2 can directly bind to C. neoformans, establishing it as a bona fide fungal pattern recognition receptor. Critically, disruption of β-1,6-glucan, a component of the cryptococcal cell wall, abolished this binding, identifying the likely molecular ligand. These findings suggest that C. neoformans may exploit the TREM2-DAP12 signaling axis to dampen host immunity, potentially contributing to the pathogen's ability to establish persistent infections, particularly in immunocompromised individuals.
What's missing
As a preprint, this study has not yet undergone peer review. The work is primarily conducted in murine models, and it remains unclear whether TREM2-DAP12 signaling plays an equivalent inhibitory role in human disease. The study does not address whether therapeutic blockade of TREM2 or DAP12 improves outcomes without causing off-target immunopathology, nor does it clarify whether β-1,6-glucan is the sole cryptococcal ligand for TREM2.
What different sources said
- bioRxivCenter
TREM2 drives monocyte-derived macrophage responses to Cryptococcus neoformans
Related
Gut Bacteria Enzyme Found to Break Down Heat-Processed Food Compounds, Producing Novel Biogenic Amines
Researchers have discovered that an enzyme in common gut bacteria can degrade N-epsilon-carboxymethyllysine (CML), a compound formed during thermal food processing, producing previously unknown biogenic amines. The enzyme, ornithine decarboxylase SpeC from enterobacteria, acts on CML and related modified lysine derivatives through a low-level 'underground' catalytic activity. This finding suggests a previously unrecognized communication axis between thermally processed dietary compounds and gut microbial physiology, with potential implications for host health.
Full-Length Gene Sequencing Reveals Two Distinct Bacterial Communities in Black-Legged Ticks Expanding Into Canada
Researchers used Oxford Nanopore full-length 16S rRNA gene sequencing to characterize the microbiome of Ixodes scapularis black-legged ticks collected in Nova Scotia, Canada, distinguishing between tick-adapted bacteria and environmentally acquired bacteria. The study comes as I. scapularis — the primary vector of Lyme disease — is rapidly expanding northward into Canada due to climate change. The findings suggest that environmentally derived bacteria in tick microbiomes are not mere contamination, which has implications for how tick microbiome data is collected and interpreted across surveillance studies.
Study Identifies Metabolic Link Between Cell Envelope Stress and Biofilm Formation in Bacteria
Researchers have discovered that the metabolite acetyl-CoA directly inhibits enzymes that degrade the bacterial signaling molecule c-di-GMP, connecting cell envelope biosynthesis stress to biofilm formation in Pseudomonas aeruginosa. The study found that sub-inhibitory concentrations of antibiotics targeting early peptidoglycan biosynthesis — but not other antibiotic classes — elevate c-di-GMP levels by reducing phosphodiesterase activity, with acetyl-CoA competing for the enzyme active site. Because the relevant enzyme domain is broadly conserved across bacterial species, this checkpoint mechanism may be widespread and could have implications for understanding antibiotic-induced biofilm responses.