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Updated: Jan 30, 2026
Immunometabolic Circuits in Infection for Advancing Host Directed Therapies
Published on: September 13, 2024
Immunometabolism at the interface between macrophages and pathogens
David G Russell1, Lu Huang2, Brian C VanderVen2
1Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. dgr8@cornell.edu.
Abstract:
It is generally regarded that the progression of an infection within host macrophages is the consequence of a failed immune response. However, recent appreciation of macrophage heterogeneity, with respect to both development and metabolism, indicates that the reality is more complex. Different lineages of tissue-resident macrophages respond divergently to microbial, environmental and immunological stimuli. The emerging picture that the developmental origin of macrophages determines their responses to immune stimulation and to infection stresses the importance of in vivo infection models. Recent investigations into the metabolism of infecting microorganisms and host macrophages indicate that their metabolic interface can be a major determinant of pathogen growth or containment. This Review focuses on the integration of data from existing studies, the identification of challenges in generating and interpreting data from ongoing studies and a discussion of the technologies and tools that are required to best address future questions in the field.
Insights
Macrophage heterogeneity complicates infection outcomes, challenging the view of a failed immune response. Understanding macrophage development and metabolism is key to controlling pathogen growth.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Traditionally, infection progression in macrophages is attributed to immune failure.
- Macrophage heterogeneity in development and metabolism reveals a more complex scenario.
- Different tissue-resident macrophage lineages exhibit varied responses to stimuli.
Purpose of the Study:
- To review current understanding of macrophage heterogeneity in infection.
- To highlight the role of macrophage development and metabolism in infection outcomes.
- To discuss challenges and future directions in studying host-pathogen interactions.
Main Methods:
- Integration of existing research data.
- Analysis of ongoing studies on macrophage responses.
- Discussion of technological and methodological requirements.
Main Results:
- Macrophage developmental origin influences immune and infection responses.
- The metabolic interplay between host macrophages and microbes is critical for pathogen control.
- In vivo infection models are essential for accurate interpretation of macrophage behavior.
Conclusions:
- Macrophage heterogeneity is a crucial factor in determining infection progression.
- Targeting the host-pathogen metabolic interface offers potential therapeutic strategies.
- Future research requires advanced tools and in vivo models to fully elucidate macrophage roles in infection.
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