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Published on: May 2, 2018
Distal Consequences of Mucosal Infections in Intestinal and Lung Inflammation
Felipe Melo-González1,2,3, Javiera Sepúlveda-Alfaro1,2, Bárbara M Schultz1,2
1Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile.
Abstract:
Infectious diseases are one of the leading causes of morbidity and mortality worldwide, affecting high-risk populations such as children and the elderly. Pathogens usually activate local immune responses at the site of infection, resulting in both protective and inflammatory responses, which may lead to local changes in the microbiota, metabolites, and the cytokine environment. Although some pathogens can disseminate and cause systemic disease, increasing evidence suggests that local infections can affect tissues not directly invaded. In particular, diseases occurring at distal mucosal barriers such as the lung and the intestine seem to be linked, as shown by epidemiological studies in humans. These mucosal barriers have bidirectional interactions based mainly on multiple signals derived from the microbiota, which has been termed as the gut-lung axis. However, the effects observed in such distal places are still incompletely understood. Most of the current research focuses on the systemic impact of changes in microbiota and bacterial metabolites during infection, which could further modulate immune responses at distal tissue sites. Here, we describe how the gut microbiota and associated metabolites play key roles in maintaining local homeostasis and preventing enteric infection by direct and indirect mechanisms. Subsequently, we discuss recent murine and human studies linking infectious diseases with changes occurring at distal mucosal barriers, with particular emphasis on bacterial and viral infections affecting the lung and the gastrointestinal tract. Further, we discuss the potential mechanisms by which pathogens may cause such effects, promoting either protection or susceptibility to secondary infection.
Insights
The gut microbiota influences immune responses at distant sites like the lungs, impacting infectious disease outcomes. Understanding the gut-lung axis is crucial for managing infections and preventing secondary complications.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Infectious diseases cause significant global morbidity and mortality, particularly in vulnerable populations.
- Local infections can trigger systemic effects and influence distant mucosal barriers, such as the gut and lung.
- The gut-lung axis describes bidirectional communication between the gastrointestinal tract and lungs, mediated by microbiota and metabolites.
Purpose of the Study:
- To explore the role of gut microbiota and metabolites in maintaining homeostasis and preventing enteric infections.
- To review evidence linking infectious diseases with alterations at distal mucosal sites, focusing on the gut-lung axis.
- To discuss mechanisms by which pathogens influence distant tissues and susceptibility to secondary infections.
Main Methods:
- Review of current murine and human studies on infectious diseases and mucosal barrier interactions.
- Analysis of epidemiological data on linked lung and gastrointestinal infections.
- Discussion of molecular and immunological mechanisms underlying the gut-lung axis.
Main Results:
- Gut microbiota and metabolites are vital for local immune homeostasis and protection against enteric pathogens.
- Infections in one mucosal site (e.g., gut) can significantly impact distant sites (e.g., lung) through the gut-lung axis.
- Pathogens can modulate immune responses at distal sites, potentially increasing or decreasing susceptibility to other infections.
Conclusions:
- The gut-lung axis is a critical factor in infectious disease pathogenesis and immune response.
- Further research into the gut-lung axis mechanisms can reveal novel therapeutic targets for infectious diseases.
- Understanding these interactions is essential for managing infections in high-risk populations.
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