Toll-like receptors(TLRs)
Cell surface
and endosomes
- Recognize bacterial, viral, fungal and self-derived ligands (e.g., LPS, flagellin, dsRNA, CpG DNA).
- Activate NF-κB, MAPK and/or IRF pathways.
- Induce inflammatory cytokines and type I interferons.
Microbes
(PAMPs)
(PAMPs)
Damaged or stressed cells
(DAMPs)
(DAMPs)
Dendritic cell
(sentinel of the immune system)
(sentinel of the immune system)
Pattern
Recognition
Receptors
How the immune system senses infection and danger.
Pattern recognition receptors (PRRs) are germline-encoded sensors of the innate immune system. They recognize conserved molecular patterns from microbes (pathogen-associated molecular patterns, PAMPs) and signals released by damaged or stressed cells (damage-associated molecular patterns, DAMPs), helping to initiate innate defenses and shape adaptive immunity.
Explore the innate immune system →PRRs at a glance
What they are
Germline-encoded receptors of the innate immune system.
Where they are
Found on the cell surface, in endosomes, or in the cytosol of many immune cells.
Main role
Recognize PAMPs and DAMPs and activate signaling pathways that initiate immune responses.
Evolutionary advantage
Detect conserved microbial and danger signals to provide rapid, broad protection.
Two types of signals
PAMPs
(Pathogen-associated molecular patterns)• Conserved structures from microbes (bacteria, viruses, fungi, parasites)
(e.g., LPS, flagellin)
DAMPs
(Damage-associated molecular patterns)• Molecules released by stressed, damaged or dying cells
The major PRR families
Different PRR families recognize distinct microbial or danger signals and are located in different cellular compartments.
C-type lectin receptors(CLRs)
Cell surface
- Recognize carbohydrate structures (e.g., β-glucans from fungi).
- Important for antifungal immunity and also sense self-derived ligands.
- Activate NF-κB and other pathways.
NOD-like receptors(NLRs)
Cytosol
- Sense bacterial components (e.g., peptidoglycan) and danger signals.
- Some NLRs (e.g., NLRP3) form inflammasomes.
- Activate caspase-1 and promote IL-1β and IL-18 production.
RIG-I-like receptors(RLRs)
Cytosol
- Detect viral RNA in the cytosol.
- Activate IRF3/IRF7 and NF-κB pathways.
- Induce type I interferons and antiviral responses.
AIM2-like receptors(ALRs)
Cytosol
- AIM2 detects cytosolic DNA.
- Forms an inflammasome with caspase-1.
- Induces IL-1β and IL-18 and can trigger pyroptosis.
cGAS–STING pathway
Cytosol
- cGAS senses cytosolic DNA and produces cGAMP.
- STING activates IRF3 and NF-κB pathways.
- Induces type I interferons and inflammatory cytokines.
From recognition to immune response
PRR signaling triggers a coordinated sequence of events that link innate and adaptive immunity.
1Detection
of PAMPs or DAMPs
PRRs recognize conserved microbial or danger signals at the cell surface, in endosomes or in the cytosol.
2Receptor activation
and signaling
Adaptor proteins
Recruitment of adaptor proteins (e.g., MyD88, TRIF, STING) and activation cascades.
3Activation of
transcription factors
Activation of NF-κB, MAPK and/or IRF3/7 leads to changes in gene expression.
4Production of immune
mediators
Cytokines (e.g., TNF-α, IL-6)
Chemokines (e.g., CCL2, CXCL10)
Type I interferons (IFN-α/β)
Chemokines (e.g., CCL2, CXCL10)
Type I interferons (IFN-α/β)
5Immune response
and link to adaptive immunity
Recruitment and activation of immune cells and enhanced antigen presentation help initiate adaptive immunity.
Where PRRs are located in the cell
Why PRRs matter
PRRs provide essential protection and help maintain overall health.
Rapid detection
Recognize microbial and danger signals before infection is established.
Fight infections
Activate antimicrobial responses and antiviral defenses.
Initiate inflammation
Drive production of cytokines and chemokines to recruit immune cells.
Bridge to adaptive immunity
Help activate dendritic cells and enhance T and B cell responses.
Sense tissue damage
Detect danger signals from stressed or injured cells and help with tissue repair.
When PRR signaling goes wrong
Imbalanced PRR activation can contribute to disease.
Excessive or persistent activation
- Can contribute to chronic inflammation and immune-mediated diseases (e.g., autoimmune disease, cardiovascular disease, metabolic disorders).
- May be driven by persistent infection, sterile inflammation or dysregulated self-sensing.
Insufficient or impaired signaling
- Can lead to increased susceptibility to infections (e.g., severe viral or bacterial infections).
- Genetic deficiencies in PRR pathways can cause primary immunodeficiencies.
PRRs and aging
Aging can alter innate immune sensing and PRR signaling, contributing to a state of low-grade inflammation (inflammaging) and changes in responses to infections and vaccines.
Learn more about aging & immunity →Key takeaways
- PRRs are germline-encoded sensors that detect microbial and danger signals.
- They trigger inflammatory and antiviral responses and help shape adaptive immunity.
- Different PRR families recognize distinct ligands and are found in different cellular locations.
- Balanced PRR signaling is essential for protection; both excessive and insufficient signaling can contribute to disease.
- PRR function can change with age and influence susceptibility to infection and inflammation.
Selected sources and references
- Takeuchi & Akira, 2010 — Pattern recognition receptors and inflammation
- Janeway et al., 2001 — Induced innate responses to infection
- Furman et al., 2019 — Chronic inflammation in the etiology of disease across the life span
Artwork illustrates the main mechanisms schematically; molecular sizes, colors and distances are not literal.