PAMPs and DAMPs: What is the Same and What is Different About These Molecules?

By Victoria Osinski

What are PAMPs and DAMPs

Inflammation results from stimuli signaling damage or infection. The immune system inflammatory response can be beneficial or harmful depending on the type and duration of stimuli. The source, structure, and abundance of these stimuli vary quite a bit. One major category of inflammatory stimulation, or "signal 0s" is the family of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).^1,2 These patterns are found on bacterial cell walls, DNA, lipoproteins, carbohydrates, or other structures. While many DAMPs and PAMPs have been identified, they stimulate inflammatory responses in context-specific ways leaving room for much more research on their signaling mechanisms.

PAMPs vs. DAMPs: What’s the Difference?

PAMPs are derived from microorganisms and thus drive inflammation in response to infections.² One well-known PAMP is lipopolysaccharide (LPS), which is found on the outer cell wall of gram-negative bacteria.³ DAMPs are derived from host cells including tumor cells, dead or dying cells, or products released from cells in response to signals such as hypoxia. Because they are derived from host materials, DAMPs induce what’s known as sterile inflammatory responses. DAMPs are often created or exposed in environments of trauma, ischemia, or tissue damage and do not require pathogenic infection.^2,4 These environments are created in settings such as myocardial infarction, cancer, autoimmune disease, and atherosclerosis.⁵

Pattern Recognition Receptors: Signaling Downstream of PAMPs and DAMPs

PAMPs and DAMPs bind to pattern recognition receptors, which include Toll-like receptors (TLRs), cytoplasmic NOD-like receptors (NLRs), intracellular retinoic acid-inducible gene-I)-like receptors (RLR), transmembrane C-type lectin receptors, and absent in melanoma 2-like receptors (AIM2).^3,5 Cell types expressing pattern recognition receptors include innate immune cells such as macrophages, monocytes, dendritic cells, and mast cells but also non-immune cells such as epithelial cells and fibroblasts.^1,2 Pattern recognition receptor-ligand binding and their concomitant conformational changes prompt a cascade of downstream signaling that result in transcriptional changes as well as post-translational modifications.³ Broadly, pattern recognition receptor engagement results in signals that prompt leukocyte recruitment.³

TLR4 was detected in immersion fixed RAW 264.7 mouse monocyte/macrophage cell line using Rat Anti-Mouse TLR4 Monoclonal Antibody (Catalog # MAB2759) at 10 µg/mL for 3 hours at room temperature. Cells were stained using the NorthernLights™ 557-conjugated Anti-Rat IgG Secondary Antibody (red; Catalog # NL013) and counterstained with DAPI(blue). Specific staining was localized to the cell surface.


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Pattern Recognition Receptor Responses are Context-Dependent

Pattern recognition receptors are capable of recognizing a variety of molecular patterns, which in turn induce a receptor-dependent response. A single pattern recognition receptor can recognize multiple PAMPs and DAMPs and the structural and molecular mechanisms mediating how this happens are still being studied.⁵ Furthermore, simultaneous signaling within the same cell can modulate downstream responses to pattern recognition receptor engagement. For example, cytokines can stimulate downstream signaling that may be complimentary, amplifying, or inhibitory to pattern recognition receptor signaling pathways.¹ Thus, such complexities make the study of PAMP- and DAMP-induced inflammatory immune responses complicated but quite fascinating.

Victoria (Tori) Osinski, Doctoral Candidate  
University of Virginia
Victoria studies cellular mechanisms regulating vascular growth during peripheral artery disease and obesity.

References

1.  Newton K, Dixit VM. Signaling in innate immunity and inflammation. Cold Spring Harb Perspect Biol. ;4(3):a006049. Published. doi:10.1101/cshperspect.a006049
2. Tang D, Kang R, Coyne CB, Zeh HJ, Lotze MT. PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunol Rev. 2012;249(1):158–175. doi:10.1111/j.1600-065X.2012.01146.x
3. Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev. 2009;22(2):240–273. doi:10.1128/CMR.00046-08
4. Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol. 2007 Jan;81(1):1-5.
5. Schaefer L. Complexity of Danger: The Diverse Nature of Damage-associated Molecular Patterns. J Biol Chem. 2014;289(51):35237–35245.