Biology subjects

Chervonsky, A.

Publications and source records attributed to Chervonsky, A..

5 recordsLinked to original sources

bioRxiv2026

Host genetics determines the fate of the Lactobacillaceae population in the small intestine

Whereas innate pattern recognition receptors bind evolutionary conserved moieties shared by diverse groups of microbes, control over closely related microorganisms is likely based on different principles and can be sensitive to genetic variation of the host. While the influence of host genetics on intestinal microbiome composition has been growing in appreciation, understanding of polymorphic mechanisms that regulate individual bacterial lineages requires complex approaches. Using gnotobiotic mouse monocolonized with Ligilactobacillus murinus (ASF361), we found that C57BL/6J (B6) mice harbored significantly more intestinal ASF361 (or other Lactobacillaceae genera) than did BALB/cJ (BALB/c) mice. The difference in ASF361 abundance was independent of adaptive immunity and bacteriotoxic factors. In B6 mice, ASF361 occupied ileal crypts, showed greater expression of adhesion-related molecules, and enriched expression of carbohydrate-metabolism pathways, whereas in BALB/c mice, ASF361 remained largely luminal and enriched expressed genes associated with starvation and stress. These findings highlight the importance of host genetic variation in shaping microbial colonization and suggest that such variation should be considered when evaluating probiotic strains and microbiota transplantation.

microbiology↗

bioRxiv2026

immgenT: A Comprehensive Reference of Convergent T-cell States in the Mouse

The immgenT collaborative project generated a comprehensive molecular atlas of T cells spanning virtually all mouse organs and disease states, profiling ~800,000 cells from 750 samples with RNA, 128-plex surface protein, and {beta}TCR sequence. Applying a deep generative model to joint RNA and protein data defined the landscape of T-cell states organized into eight lineages and 107 robust clusters, integrating similar cells from different contexts, and resolving prior nomenclatures. Analysis of effector molecules, transcription factors and modules showed that both immunological functions and regulatory programs are shared across cell states. This framework provides a stable, reusable reference, demonstrated by computationally integrating 16 external datasets from diverse biological contexts. A set of public web tools supports browsing of these data and mapping of any dataset onto the immgenT framework. These results propose a molecular classification of T cells organized around a set of shared states reused across immunological contexts.

immunology↗

bioRxiv2023

Retroviral infection and commensal bacteria dependently alter the metabolomic profile in a sterile organ

Both viruses and bacteria produce pathogen associated molecular patterns that may affect microbial pathogenesis and anti-microbial responses. Additionally, bacteria produce metabolites while viruses could change metabolic profiles of the infected cells. Here, we used an unbiased metabolomics approach to profile metabolites in spleens and blood of Murine Leukemia Virus-infected mice monocolonized with Lactobacillus murinus to show that viral infection significantly changes the metabolite profile of monocolonized mice. We hypothesize that these changes could contribute to viral pathogenesis or to the host response against the virus and thus, open a new avenue for future investigations.

microbiology↗

bioRxiv2022

Gut commensal bacteria enhance pathogenesis of a tumorigenic murine retrovirus

The influence of the microbiota on viral transmission and replication is well appreciated. However, its impact on retroviral pathogenesis outside of transmission/replication control remained unknown. Using Murine Leukemia Virus (MuLV), we found that some commensal bacteria promoted the development of leukemia induced by this retrovirus. The promotion of leukemia development by commensals was due to suppression of the adaptive immune response through upregulation of several negative regulators of immunity. These negative regulators included Serpinb9b and Rnf128, which are associated with a poor prognosis of some spontaneous human cancers. Upregulation of Serpinb9b was mediated by sensing of bacteria by NOD1/NOD2/RIPK2 pathway. This work describes a novel mechanism by which the microbiota enhances tumorigenesis within gut-distant organs and points at potential new targets for cancer therapy.

microbiology↗

bioRxiv2018

T cells instruct dendritic cells to produce inflammasome independent IL-1β causing systemic inflammation

While IL-1{beta} is critical for anti-microbial host defense, it is also a key mediator of autoimmune inflammation. Inflammasome activation following pathogenic insults is known to result in IL-1{beta} production. However, the molecular events that produce IL-1{beta} during T cell driven autoimmune diseases remain unclear. Here, we have discovered an inflammasome-independent pathway of IL-1{beta} production that is triggered upon cognate interactions between dendritic cells and effector CD4 T cells. Analogous to inflammasome activation, this \"T cell-instructed IL-1{beta} also relies on two independent signaling events. TNF produced by activated CD4 T cells engages TNFR signaling on DCs leading to pro-IL-1{beta} synthesis. Subsequently, FasL, also expressed by effector CD4 T cells, engages Fas on DCs leading to caspase-8 dependent pro-IL-1{beta} cleavage. Remarkably, this two-step mechanism is completely independent of pattern recognition receptor activation. IL-1{beta} produced upon cognate DC-effector CD4 T cell interaction causes wide spread leukocyte infiltration, a hallmark of systemic inflammation as well as autoimmune pathology. This study has uncovered a novel feature of DC-T cell cross-talk that allows for active IL-1{beta} secretion independent of innate sensing pathways and provides a mechanistic explanation for IL-1{beta} production and its downstream consequences in CD4 T cell driven autoimmune pathology.

immunology↗