Biology subjects

Hellmann, M. J.

Publications and source records attributed to Hellmann, M. J..

4 recordsLinked to original sources

bioRxiv2026

Chitin oligomers induce atypical NLRP3 inflammasome activation and innate immune training

Chitin is a highly abundant poly- N-acetyl-glucosamine (GlcNAc) and linked to immune recognition of fungal infections and asthma in humans. Ubiquitous in fungi and insects, in mammals and plants chitin represents a microbe-associated molecular pattern (MAMP) and whereas highly polymeric chitin is insoluble and immunologically inert, soluble chitin oligomers of 6 to 15 GlcNAc activate immediate pro-inflammatory cytokine release via TLR2 in human immune cells. However, TLR2 ligands do not the most typical activators of the NLRP3 inflammasome pathway or innate immune training, a phenomenon of long-term immunological remodeling. Here we show that especially 16-20 GlcNAc long chitin oligomers activate NLRP3-dependent IL-1{beta} and IL-18 release in human myeloid immune cells in an atypical, phagocytosis-dependent manner. Moreover, phagocytosis and methyl transferase activity were essential for innate immune training, by which the same chito-oligomer-training enhanced TNF release in primary murine and human immune cells. Collectively, this suggests that oligomer length impacts on the immune features of chitin which can be customized using glycan assembly.

immunology↗

bioRxiv2025

Domain gain or loss in fungal chitinases drives ecological specialization toward antagonism or immune suppression

The evolutionary origins of fungal effector proteins remain poorly understood, particularly how structural changes reprogram antimicrobial enzymes into host-adapted immune suppressors. Here, we show that domain modularity drives ecological specialization in chitinase effectors of the beneficial root endophyte Serendipita indica. The GH18 chitinase SiCHIT, which carries a C-terminal carbohydrate-binding module (CBM5), is expressed during fungal competition and antagonizes the fungal pathogen Bipolaris sorokiniana in the rhizosphere, thereby protecting plant roots. Deletion of the CBM5 abolishes this antifungal activity, while fusion of CBM5 to the CBM5-lacking paralog SiCHIT2 restores pathogen inhibition. In contrast, SiCHIT2 is induced during root colonization and suppresses chitin-triggered reactive oxygen species production, promoting immune evasion and host compatibility. These results identify CBM5 as a modular determinant of effector function, switching chitinase activity between microbial antagonism and host immune suppression. Our findings support an evolutionary scenario in which effector function in planta arises through domain loss and transcriptional divergence from an antimicrobial precursor, consistent with transitions along the saprotrophy-to-symbiosis continuum. Significance StatementEffector proteins play key roles in shaping fungal interactions with both plant hosts and microbial competitors, yet how these functions evolve remains unclear. Here, we show that structural domain modularity enables ecological specialization of two paralogous chitinases arising from gene duplication in the root endophyte Serendipita indica. Through domain deletion and fusion, we demonstrate that a carbohydrate-binding module (CBM5) determines whether a chitinase functions in microbial antagonism or immune evasion. Our findings provide mechanistic evidence for effector diversification via domain loss and transcriptional divergence, supporting an evolutionary trajectory from antimicrobial activity to host adaptation. This work advances our understanding of how modular architecture drives effector evolution and niche specialization in symbiotic fungi. HighlightsO_LIGain or loss of a CBM5 binding domain drives effector specialization between fungal antagonism and immune suppression C_LIO_LICBM5 acts as a modular determinant enabling antifungal activity in the GH18 chitinase SiCHIT C_LIO_LIThe CBM5-lacking paralog SiCHIT2 suppresses host immunity and promotes root colonization C_LIO_LIFunctional divergence following gene duplication illustrates evolutionary repurposing of an antimicrobial enzyme into an immune-suppressive effector C_LI

plant biology↗

bioRxiv2023

Time-resolved transcriptomics reveal a mechanism of host niche defense: beneficial root endophytes deploy a host-protective antimicrobial GH18-CBM5 chitinase

Associations between plants and beneficial root-endophytic fungi enhance plant performance by improving nutrient uptake, abiotic stress tolerance and disease resistance. To successfully colonize different host plants and defend their host niche against competing microbes, but also to cooperate with beneficial bacterial members of the microbiota, root endophytes such as Sebacinales secrete a multitude of tightly regulated effector-proteins and carbohydrate-active enzymes. However, the functions, specificity, and regulation of these proteins remain poorly understood. In this study, we employ time-resolved transcriptomics to analyse the gene expression profiles of two Sebacinales members interacting with organisms from different kingdoms of life. We identified crucial genes for plant colonization and intermicrobial competition, including a fungal GH18-CBM5 chitinase specifically upregulated in response to the phytopathogenic fungus Bipolaris sorokiniana. This chitinase protects the plant hosts against the pathogen, reducing fungal biomass and disease symptoms in barley and Arabidopsis thaliana. Our findings shed light on interaction partner specific gene expression in Sebacinales endophytes, with potential applications in enhancing plant health and resilience. Bullet pointsO_LIBoth Serendipita indica (Si) and Serendipita vermifera (Sv) show similar transcriptional responses to three host species and the phytopathogen Bipolaris sorokiniana (Bs), indicating common interaction principles between Sebacinales and plant hosts or fungi. C_LIO_LIThese shared mechanisms involve the activation of effector genes like small secreted proteins and carbohydrate-active enzymes. C_LIO_LICooperation with beneficial bacteria elicits only minimal transcriptomic alterations in Sebacinales compared to plants and Bs. C_LIO_LISebacinales respond to Bs by upregulating a specific GH18-CBM5 chitinase unique to Basidiomycota within the fungal kingdom, inhibiting Bs growth and reducing disease symptoms in Arabidopsis thaliana and barley. C_LI

microbiology↗

bioRxiv2022

Transkingdom mechanism of MAMP generation by chitotriosidase (CHIT1) feeds oligomeric chitin from fungal pathogens and allergens into TLR2-mediated innate immune sensing

Chitin is a highly abundant polysaccharide in nature and linked to immune recognition of fungal infections and asthma in humans. Ubiquitous in fungi and insects, chitin is absent in mammals and plants and, thus, represents a microbe-associated molecular pattern (MAMP). However, the highly polymeric chitin is insoluble, which potentially hampers recognition by host immune sensors. In plants, secreted chitinases degrade polymeric chitin into diffusible oligomers, which are fed to innate immune receptors and co-receptors. In human and murine immune cells, a similar enzymatic activity was shown for human chitotriosidase (CHIT1) and oligomeric chitin is sensed via an innate immune receptor, Toll-like receptor (TLR) 2. However, a complete system of generating MAMPs from chitin and feeding them into a specific receptor/co-receptor-aided sensing mechanism has remained unknown in mammals. Here, we show that the secreted chitinolytic host enzyme, CHIT1, converts inert polymeric chitin into diffusible oligomers that can be sensed by TLR1-TLR2 co-receptor/receptor heterodimers, a process promoted by the lipopolysaccharide binding protein (LBP) and CD14. Furthermore, we observed that Chit1 is induced via the {beta}-glucan receptor Dectin-1 upon direct contact of immortalized human macrophages to the fungal pathogen Candida albicans, whereas the defined fungal secreted aspartyl proteases, Sap2 and Sap6, from C. albicans were able to degrade CHIT1 in vitro. Our study shows the existence of an inducible system of MAMP generation in the human host that enables contact-independent immune activation by diffusible MAMP ligands with striking similarity to the plant kingdom. Moreover, this study highlights CHIT1 as a potential therapeutic target for TLR2-mediated inflammatory processes that are fueled by oligomeric chitin.

immunology↗