The immediate protective response to microbial challenge
José M González-Navajas1, Mary P Corr, Eyal Raz
1Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Hospital General de Alicante, Alicante, Spain; Division of Rheumatology, Allergy and Immunology, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Abstract:
The innate immune system detects infection and tissue injury through different families of pattern-recognition receptors (PRRs), such as Toll-like receptors. Most PRR-mediated responses initiate elaborate processes of signaling, transcription, translation, and secretion of effector mediators, which together require time to achieve. Therefore, PRR-mediated processes are not active in the early phases of infection. These considerations raise the question of how the host limits microbial replication and invasion during this critical period. Here, we examine the crucial defense mechanisms, such as antimicrobial peptides or extracellular traps, typically activated within minutes of the initial infection phase, which we term the "immediate protective response". Deficiencies in different components of the immediate protective response are often associated with severe and recurrent infectious diseases in humans, highlighting their physiologic importance.
Insights
The innate immune system uses rapid, immediate protective responses, not just slower Toll-like receptor pathways, to fight infections early on. These early defenses are vital for preventing severe and recurrent infectious diseases.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- The innate immune system relies on pattern-recognition receptors (PRRs), like Toll-like receptors, to detect pathogens and injury.
- PRR-mediated responses involve complex signaling, transcription, and translation, which are too slow for immediate infection control.
- A critical gap exists in understanding host defenses during the initial minutes of infection.
Purpose of the Study:
- To investigate the host's defense mechanisms active within minutes of infection.
- To define and characterize the "immediate protective response" as a distinct arm of innate immunity.
- To highlight the physiological importance of these rapid responses in preventing microbial invasion.
Main Methods:
- Review and analysis of existing literature on early host defense mechanisms.
- Examination of antimicrobial peptides and extracellular traps as key components of the immediate response.
- Correlation of deficiencies in immediate protective responses with clinical outcomes in infectious diseases.
Main Results:
- The immediate protective response, including antimicrobial peptides and extracellular traps, acts within minutes of infection.
- These rapid mechanisms are distinct from and precede slower PRR-mediated signaling pathways.
- Defects in the immediate protective response are linked to severe and recurrent human infections.
Conclusions:
- The immediate protective response is a crucial, evolutionarily conserved defense system.
- Understanding this rapid response is essential for combating infectious diseases.
- Targeting or bolstering immediate protective mechanisms may offer new therapeutic strategies.
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