Microbial Secretion Systems and Host Immune Responses: From Symbiosis to Pathogenesis

The vertebrate immune system has co-evolved alongside an extraordinary diversity of microorganisms, many of which deploy specialised secretion machineries to actively engage, manipulate, or evade host immune defences. Bacterial type III, IV, and VI secretion systems, as well as emerging secretion pathways in fungi and other microbes, deliver effector proteins directly into host cells, where they interfere with innate immune signalling, subvert pattern recognition, suppress inflammatory responses, or redirect adaptive immunity. Critically, secretion-mediated immune modulation is not a strategy exclusive to pathogens: commensal and symbiotic microorganisms exploit homologous machineries to negotiate immune tolerance, shape microbiome composition, and maintain host homeostasis. The functional outcome — mutualism or virulence — is therefore determined not by the secretion apparatus alone, but by the specific effector repertoire it deploys and the immune circuits it engages.

Despite growing insight into individual effectors, key questions remain unresolved. How do structurally conserved secretion systems drive such divergent immune outcomes across pathogens, commensals, and symbionts? What molecular logic governs secretion system-mediated immune evasion versus immune activation? How does effector repertoire diversification across strains and species shape long-term host–microbiome immune homeostasis? Addressing these questions requires an integrated perspective that bridges structural microbiology, effector biology, and systems immunology.

This Research Topic invites contributions that place microbial secretion systems at the centre of host immune biology — examining how the architecture, diversity, and evolution of these molecular machines, and the effectors they deliver, determine immune outcomes across the full spectrum from symbiosis to pathogenesis.

This Research Topic welcomes mechanistic, comparative, structural, computational, and translational studies exploring how microbial secretion systems and secreted effectors shape host immune recognition, immune evasion, mucosal homeostasis, symbiosis, dysbiosis, and infectious disease progression. Structural and computational submissions are welcome where they directly address effector–host immune interactions; studies focused solely on microbial physiology or secretion system architecture without an immune readout fall outside the scope of this topic.

Topics of interest include, but are not limited to, the following themes:

o Molecular mechanisms of secretion system-mediated immune evasion and immune activation

o Effector protein function: subversion of innate immune sensors, inflammasomes, and cytokine networks

o Secretion system-dependent modulation of dendritic cell, macrophage, and neutrophil function

o Effector repertoire diversification and its consequences for adaptive immunity and immune memory

o Role of commensal and symbiont secretion systems in microbiome-immune crosstalk and homeostasis

o Secretion systems in biofilm formation and chronic infection: secreted adhesins, immune-modulatory factors, and effector-driven immune tolerance in persistent and recurrent infections

o Secretion-related effector mechanisms in fungal and parasitic host–immune interactions

o Extracellular vesicles and non-classical secretion pathways as vehicles for immune-active microbial molecules

o Comparative genomics and functional diversity of secretion systems across host-associated microbes

o Structural biology of secretion machineries and effector–host target interactions

o Multi-omics, single-cell, and AI-driven approaches to mapping effector–immune interactomes

o Antimicrobial resistance and secretion system evolution: links between virulence–resistance co-selection, horizontal gene transfer, and immune escape

o Experimental models for studying secretion system–immune interactions, including organoids, gnotobiotic animals, zebrafish, CRISPR screens, and spatial transcriptomics

o Translational perspectives: targeting secretion systems in infectious, inflammatory, and autoimmune disease

This Research Topic particularly welcomes Original Research, Review, Mini Review, Perspective, Hypothesis and Theory, Systematic Review, Methods, and Technology and Code articles.