The role of lipopolysaccharide in the development of atopy in humans
Open accessAbstract
Summary: Atopy is a highly prevalent condition and remains the single biggest risk factor for asthma. Although atopy has a heritable component, the time frame of the increase in the prevalence indicates that it is not due to genetic factors alone. The relationship between allergen exposure and sensitization is complex. Lipopolysaccharide (LPS) and its bioactive moiety endotoxin are common to all gram‐negative bacteria, and have been used as a surrogate of microbial load. Endotoxin can be readily measured in dust collected from homes. Some studies have demonstrated a clear inverse dose–response relationship between exposure to endotoxin and the risk of atopy but this finding has not been reproduced in all studies. Our innate immune system recognizes LPS readily via the LPS signal transduction pathway, which has the trimolecular complex of CD14/TLR4/MD2 at the core. A common single‐nucleotide polymorphism in the promoter region of CD14 rs2569190 C to T (CD14/−260 or CD14/−159) has been associated with elevated sCD14. Although early studies suggested that this variant was associated with more severe atopy, this finding was not uniformly replicated. It has now been demonstrated in four independent populations that high exposure to endotoxin in the domestic environment is protective against the development of atopy, but only among carriers of the C allele, that is, the environmental exposure is only relevant when taken in the context of the genotype. Furthermore, this interaction is biologically plausible. We propose that neither the environmental exposure nor the genotype in isolation is sufficient to cause complex diseases like asthma and atopy, but disease results from the one acting in the context of the other, of which CD14 and endotoxin is one example contributing to the risk for atopy. Cite this as: A. Simpson and F. D. Martinez, Clinical & Experimental Allergy, 2010 (40) 209–223.
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An inverse association between exposure to endotoxin in infancy and childhood and the development of allergic sensitization has been shown in rural and urban environments, but results have not been uniform across studies.
“Inverse association between exposure to endotoxin in infancy and childhood and the development of allergic sensitization has been shown in rural and urban environments, but the results have not been uniform between the studies.656,657”
From International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (2018) · cites this paper as [656]
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Flagged first, then by citations
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After asthma: redefining airways diseases
Pavord, I. D., Beasley, R., Agusti, A., Anderson, G. P., Bel, E., Brusselle, G., Cullinan, P., Custovic, A., Ducharme, F. M., Fahy, J. V., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(17)30879-6 · Cited by 1,073 · see citing works
Self-citationInternational Consensus Statement on Allergy and Rhinology: Allergic Rhinitis
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Disaggregating asthma: big investigation versus big data
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Self-citationThe intersect of genetics, environment, and microbiota in asthma-perspectives and challenges
Tang, H. H. F., Teo, S. M., Sly, P. D., Holt, P. G., & Inouye, M. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.08.026 · Cited by 43 · see citing works
- Authors
- Simpson, A., & Martinez, F. D.
- Affiliations
- Manchester Academic Health Science Centre (GB)
- Corresponding author
- Simpson, A.
- ORCID
- Simpson, A.
- Venue
- Clinical & Experimental Allergy
- Publisher
- Wiley
- Published
- 2010-01-11
- Volume
- 40
- Issue
- 2
- Pages
- 209-223
- ISSN
- 0954-7894 (ISSN-L)
- 1365-2222
- OpenAlex
- W2030960475
- Cited by
- 94
- References
- 105
- Citations by year
- 2025: 5 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 10 · 2015: 6 · 2014: 8 · 2013: 5 · 2012: 9
- FWCI
- 1.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical & Experimental Allergy (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Indoor Air Quality and Microbial Exposure
- Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
- Keywords
- lipopolysaccharide, endotoxin, atopy, asthma, CD14, soluble CD14, TLR4, MD-2, innate immunity, microbial exposure, dust, gene-environment interaction, allergen sensitization
- MeSH terms
- Asthma, Humans, Hypersensitivity, Lipopolysaccharides, Signal Transduction, Lipopolysaccharide Receptors, Polymorphism, Single Nucleotide
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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