Toll-like receptor 4 variants reduce airway response in human subjects at high endotoxin levels in a swine facility

Dosman, James A.; Chénard, L.; Burch, Lauranell H.; Predicala, Bernardo; Sorowski, Randine; Schneberger, David; Hurst, Tom; Kirychuk, Shelley; Gerdts, Volker; Cormier, Yvon; Rennie, Donna; Schwartz, David A.

doi:10.1016/j.jaci.2009.02.019

Cited by 31 publications

(22 citation statements)

References 37 publications

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“…25 Several studies have been performed to investigate the effects of TLR4 gene polymorphisms on occupational asthma induced by organic dust in, for example, swine farms or laboratories. 26,27 In this study, we found that workers exhibiting variants of the TLR4 promoter at -2027 AϾG and -1608 TϾC had lower work-related lower respiratory symptoms. Furthermore, an in vitro functional study indicated that the construct with ht2…”

Section: Discussionmentioning

confidence: 50%

Effect of Toll-like receptor 4 gene polymorphisms on work-related respiratory symptoms and sensitization to wheat flour in bakery workers

Cho

Kim

et al. 2011

Annals of Allergy, Asthma & Immunology

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Section: Discussionmentioning

confidence: 50%

Effect of Toll-like receptor 4 gene polymorphisms on work-related respiratory symptoms and sensitization to wheat flour in bakery workers

Cho

Kim

et al. 2011

Annals of Allergy, Asthma & Immunology

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“…Although most studies focus on swine confinement facility environments due to its strong pro-inflammatory airway response and associated lung disease manifestations, other industrial animal farm environments such as dairy farming have also been associated with a high predominance of Gram-positive and Gram-negative bacterial cell wall components (Poole et al, 2010). Roles for TLR2 that recognizes lipotechoic acids and peptidoglycans, and TLR4 that recognizes endotoxin have been described (Charavaryamath et al, 2008; Senthilselvan et al, 2009; Poole et al, 2011; Gao et al, 2013). Namely, TLR2 and TLR4 KO mice have blunted airway inflammatory responses following acute and sub-chronic swine facility dust/dust extract exposures (Charavaryamath et al, 2008; Poole et al, 2011; Bauer et al, 2013), and polymorphisms in the TLR2 and TLR4 have been associated with lung function consequences in exposed swine workers (Senthilselvan et al, 2009; Gao et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Important etiologic factors identified within the complex organic dusts include Gram-negative endotoxins, Gram-positive peptidoglycans, fungal glucans, and bacterial CpG DNA (Poole and Romberger, 2012). Moreover, important roles for Toll-like receptor (TLR)-2, TLR4, TLR9, and MyD88 have been reported to mediate organic dust-induced airway inflammatory consequences in mice and humans (Charavaryamath et al, 2008; Senthilselvan et al, 2009; Poole et al, 2011; Bauer et al, 2013; Gao et al, 2013). …”

Section: Introductionmentioning

confidence: 99%

Pattern recognition scavenger receptor A/CD204 regulates airway inflammatory homeostasis following organic dust extract exposures

Poole¹,

Anderson²,

Gleason³

et al. 2014

Journal of Immunotoxicology

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Exposure to agriculture organic dusts, comprised of a diversity of pathogen-associated molecular patterns, results in chronic airway diseases. The multi-functional class A macrophage scavenger receptor (SRA)/CD204 has emerged as an important class of pattern recognition receptors with broad ligand binding ability. Our objective was to determine the role of SRA in mediating repetitive and post-inflammatory organic dust extract (ODE)-induced airway inflammation. Wild-type (WT) and SRA knockout (KO) mice were intra-nasally treated with ODE or saline daily for 3 wk and immediately euthanized or allowed to recover for 1 wk. Results show that lung histopathologic changes were increased in SRA KO mice as compared to WT following repetitive ODE exposures marked predominately by increased size and distribution of lymphoid aggregates. After a 1-wk recovery from daily ODE treatments, there was significant resolution of lung injury in WT mice, but not SRA KO animals. The increased lung histopathology induced by ODE treatment was associated with decreased accumulation of neutrophils, but greater accumulation of CD4+ T-cells. The lung cytokine milieu induced by ODE was consistent with a TH1/TH17 polarization in both WT and SRA KO mice. Overall, our data demonstrate that SRA/CD204 plays an important role in the normative inflammatory lung response to ODE as evidenced by the enhanced dust-mediated injury viewed in the absence of this receptor.

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“…After exposure to swine confinement facility, those with the polymorphism had a significantly less decline in FEV 1 after exposure to hog confinement facility with high levels of endotoxin, suggesting a protective effect of these polymorphisms. [66] Variations in the CD14 gene have also been shown to alter response to endotoxin-exposed farmers, with those being homozygous for CD14/-159T or CD14/-1619G having less wheezing in comparison with the CC or AA genotype, respectively, in a study of farmers with high-endotoxin exposure from the Keokuk County Rural Health Cohort Study in rural Iowa. [67] Each of these studies demonstrates that polymorphisms in genotype are also highly important in the development of the asthma phenotype, both in children and adults, highlighting the importance of gene-environment interaction.…”

Section: Farming Exposure Agents: Microbial Burden and Innate Immune mentioning

confidence: 99%

Influence of farming exposure on the development of asthma and asthma-like symptoms

Wells

Poole

Romberger

2014

International Immunopharmacology

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Based upon age and type of farming exposures, a wide range of studies demonstrate either protective or deleterious effects of the farming environment on asthma. In this review, we highlight key studies supporting the concept that farming exposure protects children from asthma and atopy based on studies performed largely in European pediatric cohorts. Various types of farming in certain regions appear to have a greater effect on asthma protection, as does the consumption of unpasteurized milk. In the United State, where concentrated animal feeding operations (CAFOs) are more common, asthma is increased in children exposed especially to swine CAFOs; whereas, rates of atopy and allergy are lower in these children. We also review studies evaluating the role of farming exposures both as a child and/or as an adult on asthma seen in adults. The importance of microbes in farming environments and the contribution of various components of the innate immune system including toll-like receptors to the underlying mechanisms of asthma related to farming exposures are also reviewed.

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Toll-like receptor 4 variants reduce airway response in human subjects at high endotoxin levels in a swine facility

Cited by 31 publications

References 37 publications

Effect of Toll-like receptor 4 gene polymorphisms on work-related respiratory symptoms and sensitization to wheat flour in bakery workers

Effect of Toll-like receptor 4 gene polymorphisms on work-related respiratory symptoms and sensitization to wheat flour in bakery workers

Pattern recognition scavenger receptor A/CD204 regulates airway inflammatory homeostasis following organic dust extract exposures

Influence of farming exposure on the development of asthma and asthma-like symptoms

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