Breaking Barriers: The Breakdown of Epithelial Defenses by Pathogens

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 161

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Guest Editor
Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Avenida del Valle Sur 534, Huechuraba, Santiago 8581151, Chile
Interests: neuroimmunology; respiratory viral infection; epithelial barriers; cognition and behavior impairment; neurotrophins; neurotransmitters
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Special Issue Information

Dear Colleagues,

Epithelial and epithelial-like barriers form the first and most crucial line of defense between host tissues and the external environment or internal compartments. These include the skin, respiratory epithelium, gastrointestinal tract, urogenital epithelium, ocular and nasal mucosa, and the specialized blood–brain barrier (BBB). This tightly regulated endothelial structure protects the central nervous system, with the barriers regulating nutrient exchange, preventing microbial invasion, and initiating immune responses.

Pathogens, including bacteria, viruses, and fungi, have evolved sophisticated strategies to breach, bypass, or exploit these barriers to facilitate colonization, dissemination, and immune evasion. The breakdown of epithelial and endothelial barriers is a key step in acute infections and plays a critical role in chronic inflammation, tissue damage, and systemic diseases.

This Special Topic aims to provide a comprehensive, cross-organ perspective on how pathogens compromise epithelial integrity and the resulting consequences for infection and host health. We encourage submissions of original research, reviews, mini-reviews, and perspectives exploring molecular mechanisms, host responses, experimental models, and potential therapeutic interventions.

This Special Issue, entitled "Breaking Barriers: The Breakdown of Epithelial Defenses by Pathogens”, aims to present recent research on any aspect of the mechanisms by which pathogens interact with, disrupt, or exploit epithelial and endothelial barriers across different organ systems. Some of its focal points include, but are not limited to, the following:

  1. Mechanisms of barrier disruption by bacterial toxins, viral proteins, and fungal enzymes (e.g., tight junction degradation, endocytosis, transcytosis, apoptosis).
  2. Organ-specific and systemic perspectives, including:
  • Skin and wound-associated infections.
  • Airway epithelium in respiratory infections.
  • Gut epithelium in enteric diseases.
  • Urogenital epithelium in sexually transmitted infections.
  • Ocular and nasal barriers in mucosal pathogen entry.
  • Blood–brain barrier (BBB) disruption in neuroinvasive infections (e.g., meningitis, encephalitis)
  1. Pathogen–host signaling at epithelial and endothelial interfaces.
  2. Inflammatory and immune responses are initiated by epithelial cells upon barrier compromise.
  3. Role of the microbiota in maintaining or disrupting epithelial barrier homeostasis.

Reviews, original research, and communications are welcome. 

Dr. Karen Bohmwald
Guest Editor

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Keywords

  • epithelial barrier
  • blood–brain barrier
  • barrier breakdown
  • pathogen invasion
  • tight junctions
  • endothelial cells
  • mucosal immunity
  • host–pathogen interaction
  • epithelial remodeling
  • neuroinvasion
  • respiratory tract

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Published Papers (1 paper)

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Research

15 pages, 1952 KB  
Article
Epithelial–Macrophage Crosstalk in Host Responses to Campylobacter jejuni Infection in Humans
by Khaled Abdelaziz, Shreeya Sharma, Mostafa Naguib and Alexis Stamatikos
Microorganisms 2025, 13(12), 2808; https://doi.org/10.3390/microorganisms13122808 - 10 Dec 2025
Abstract
Interactions between Campylobacter jejuni and host immune cells have been studied using various single-cell line models, such as macrophages and intestinal epithelial cells; however, these single-cell approaches do not fully capture the complexity of the host response. Investigating the interactions between these cell [...] Read more.
Interactions between Campylobacter jejuni and host immune cells have been studied using various single-cell line models, such as macrophages and intestinal epithelial cells; however, these single-cell approaches do not fully capture the complexity of the host response. Investigating the interactions between these cell types offers a more comprehensive model for understanding Campylobacter–host dynamics. Therefore, this study aimed to investigate these interactions, specifically between intestinal epithelial cells and macrophages, using an in vitro model of C. jejuni infection. We examined whether soluble factors secreted from C. jejuni-infected HT-29 cells (human colorectal adenocarcinoma cells that express characteristics of mature intestinal cells) at 10 and 50 multiplicities of infection (MOI) influence RAW 264.7 macrophage activity, including nitric oxide (NO) production, migration, phagocytosis, bacterial killing, and the expression of cytokines (IL-6, IL-1β, TNF-α) and the chemokine CCL2. C. jejuni infection of HT-29 cells at 10 MOI induced significant IFN-γ production, a key macrophage activator. The treatment of macrophages with supernatants from HT-29 cells infected with C. jejuni significantly increased NO production, enhanced migration and phagocytic activity, and increased IL-6, TNF-α and CCL2 gene expression. However, no significant killing of phagocytosed C. jejuni was observed. On the other hand, supernatants from HT-29 cells infected with 50 MOI of C. jejuni suppressed NO production and macrophage phagocytosis, which may explain individual variations in the immune system’s ability to contain infection, potentially influenced by the infectious dose. These findings support the notion that Campylobacter can evade macrophage killing even under activated conditions. Further studies are needed to elucidate the molecular mechanisms by which Campylobacter survives within activated macrophages. Full article
(This article belongs to the Special Issue Breaking Barriers: The Breakdown of Epithelial Defenses by Pathogens)
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