Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.03.23.713660

Examining the impact of the Chlamydia muridarum-induced synthesis of IFN-β during genital tract infection

Kumar, R.·Cordova-Mendez, I.·Litika, F.·Kara, E. D.·Moiz, R.·Burgess, D.·Banerjee, A.·Derbigny, W. A.
View original source ↗Export metadata ↓

Abstract

Chlamydia trachomatis infection of the female genital tract can result in severe reproductive sequelae, including pelvic inflammatory disease, tubal scarring, and infertility. Type I interferons have been implicated in both host defense and immunopathogenesis during chlamydial infection, with conflicting conclusions across experimental systems. However, the specific contributions of individual interferon subtypes remain poorly defined. Here, we examined the role of interferon beta (IFN-{beta}) in regulating epithelial immune responses and intracellular bacterial development during Chlamydia muridarum infection. Using murine oviduct epithelial (OE) cell lines derived from wild-type, IFN{beta}-deficient, and Toll-like receptor 3 (TLR3)-deficient mice, we demonstrate that IFN-{beta} is a critical epithelial-intrinsic mediator of host defense. Loss of IFN-{beta} led to dysregulation of genes associated with inflammation, immune regulation, and fibrosis, altered chlamydial inclusion morphology, enhanced expression of bacterial genes throughout the chlamydial developmental cycle, and increased chlamydial replication. Importantly, exogenous IFN-{beta} restored both immune mediator production and bacterial control during IFN{beta}-deficiency. Parallel analyses revealed that TLR3 deficiency phenocopied IFN-{beta} loss, supporting a TLR3-IFN-{beta} signaling axis that restricts chlamydial growth. Consistent with these in vitro findings, IFN{beta}-deficient mice exhibited enhanced bacterial burden during genital tract infection. Together, these data establish IFN-{beta} as a protective epithelial mediator during chlamydial infection and demonstrate that type I interferon responses are not functionally uniform. Our findings provide a mechanistic framework to reconcile the protective role of IFN-{beta} with reports of reduced pathology in interferon-/{beta} receptor-deficient models and highlight the importance of dissecting individual interferon pathways in chlamydial immunopathogenesis. ImportanceGenital tract infection with Chlamydia trachomatis remains a leading cause of preventable infertility worldwide. Although type I interferons are widely viewed as contributors to chlamydial pathology, most studies have examined global interferon signaling rather than the roles of individual interferon subtypes. In this study, we demonstrate that interferon beta (IFN-{beta}) plays a protective, epithelial-intrinsic role during chlamydial infection by restricting bacterial development and shaping local immune responses. These findings challenge the prevailing view that type I interferons are uniformly detrimental in this setting and reveal that distinct interferon subtypes can exert opposing effects on host defense and disease outcome. By defining a TLR3-IFN-{beta} signaling axis that limits chlamydial replication, this work advances our understanding of epithelial immunity in the female genital tract and has important implications for the design of targeted immunomodulatory strategies to prevent chlamydia-induced reproductive pathology.

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kumar, R., Cordova-Mendez, I., Litika, F., Kara, E. D., Moiz, R., Burgess, D., Banerjee, A., Derbigny, W. A.. 2026-03-24. Examining the impact of the Chlamydia muridarum-induced synthesis of IFN-β during genital tract infection. https://doi.org/10.64898/2026.03.23.713660

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

A population-scale landscape of the subgingival microbiome reveals divergent routes to periodontal dysbiosis

Periodontitis is an archetypical mucosal inflammatory disease in which microbiome dysbiosis at the tooth-epithelial interface interacts with host genetic and behavioral risk factors to drive immune-mediated tissue destruction. Although subgingival microbiome compositional shifts are thought to parallel disease severity, microbiome variation at the population-level and its relationship to periodontal clinical phenotypes and disease-modifying factors remain poorly defined. Here, we use unsupervised manifold learning to map the compositional landscape of the subgingival microbiome in 1,355 adults spanning periodontal health to severe periodontitis. We identified eight latent microbiome states organized along a branching continuum from eubiosis to dysbiosis. An intermediate microbial configuration marked ecological destabilization and bifurcation into two distinct periodontitis-associated dysbiotic trajectories, distinguished by links to gingival inflammation and smoking. Although the microbiome trajectories broadly tracked periodontal destruction, a minority of individuals showed discordant microbiome-clinical phenotypes, with some individuals with periodontitis retaining otherwise eubiotic microbiomes enriched for low-abundance pathobionts, while some cases of health or mild disease had highly dysbiotic communities, suggesting distinct host susceptibility. Together, these findings define a population-scale ecological landscape of the subgingival microbiome, reveal divergent trajectories to periodontal dysbiosis, and highlight heterogeneity in the relationship between microbial community structure and clinical disease expression.

microbiology↗
bioRxiv2026

The iron-binding siderophore enterobactin is required for the response of multi-drug resistant Klebsiella pneumoniae to zinc limitation

To persist during infection Klebsiella pneumoniae must overcome nutrient iron and zinc limitation imposed by the host immune system through a process called nutritional immunity. Secreted small molecule siderophores are a major virulence determinant of Klebsiella pneumoniae pathogenesis and are presumed to overcome nutritional immunity by binding iron for bacterial acquisition. In this work, we set out to identify how a multi-drug resistant K. pneumoniae grows in zinc limited environments. Using unbiased transcriptomics, proteomics, and an arrayed transposon screen, we identified that synthesis and uptake of the siderophore enterobactin is required to allow for growth in low zinc conditions. Iron-specific chelators did not replicate this phenotype and addition of supplemental iron through heme in growth media could not complement severe growth defects of enterobactin mutant K. pneumoniae experiencing zinc limitation. Finally, zinc starvation induced enterobactin production independent of the canonical zinc uptake regulator (Zur) transcription factor suggesting an unidentified regulatory mechanism by which Gram-negative pathogens may respond to zinc stress. Together, these studies expand the role of enterobactin beyond iron regulation and highlight a previously unreported link between iron and zinc homeostasis in Klebsiella pneumoniae.

microbiology↗
bioRxiv2026

A microbiota-derived protease links phage susceptibility to host epithelial responses

Bacteriophages are major ecological drivers of gut microbial ecology, yet whether bacterial mechanisms that determine phage susceptibility have consequences for the mammalian host remains poorly understood. Here, we identify dipeptidyl peptidase 11 (Dpp11a), the predominant active serine protease of the prevalent gut commensal Phocaeicola vulgatus, as an unexpected bacterial defence factor. Dpp11a protects against environmental proteases and confers resistance to bacteriophage infection. Metatranscriptomic analyses further reveal increased expression of both dpp11a and P. vulgatus-associated phage transcripts in ulcerative colitis stool samples, indicating that both components of this interaction are transcriptionally active in disease-associated human microbiomes. Using the microfluidic gut-on-a-chip co-culture model HuMiX, we show that the absence of Dpp11 is accompanied by altered epithelial tight-junction remodelling during phage-bacterial infection. Together, our findings reveal that the consequences of bacterial phage defence can extend beyond phage-bacterium interactions to the mammalian epithelium.

microbiology↗