Urease and Helicobacter spp. Antigens in Pulmonary Granuloma

Herndon, Betty; Quinn, Tim; Wasson, Ngoc; Nzabi, Masha; Molteni, Agostino

doi:10.1016/j.jcpa.2012.06.011

Cited by 10 publications

(4 citation statements)

References 40 publications

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“…Murine models offer a viable alternative research platform for studying sarcoidosis (18). Several models have been proposed using microbes or microbe-related agents to induce granulomas (7,16,25,34,36,49,54), as well as genetic knockouts (44). Rapid resolution (14 -21 days) of granuloma formation has been a major limitation of murine models that used antigen-bound Sepharose beads (8) and methods based on bacterial proteins (22).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional survey of alveolar macrophages in a murine model of chronic granulomatous inflammation reveals common themes with human sarcoidosis

Mohan

Malur

McPeek

et al. 2018

American Journal of Physiology-Lung Cellular and Molecular Phys

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Mohan A, Malur A, McPeek M, Barna BP, Schnapp LM, Thomassen MJ, Gharib SA. Transcriptional survey of alveolar macrophages in a murine model of chronic granulomatous inflammation reveals common themes with human sarcoidosis. Am J Physiol Lung Cell Mol Physiol 314: L617-L625, 2018. First published December 6, 2017; doi: 10.1152/ajplung.00289.2017 . To advance our understanding of the pathobiology of sarcoidosis, we developed a multiwall carbon nanotube (MWCNT)-based murine model that shows marked histological and inflammatory signal similarities to this disease. In this study, we compared the alveolar macrophage transcriptional signatures of our animal model with human sarcoidosis to identify overlapping molecular programs. Whole genome microarrays were used to assess gene expression of alveolar macrophages in six MWCNT-exposed and six control animals. The results were compared with the transcriptional profiles of alveolar immune cells in 15 sarcoidosis patients and 12 healthy humans. Rigorous statistical methods were used to identify differentially expressed genes. To better elucidate activated pathways, integrated network and gene set enrichment analysis (GSEA) was performed. We identified over 1,000 differentially expressed between control and MWCNT mice. Gene ontology functional analysis showed overrepresentation of processes primarily involved in immunity and inflammation in MCWNT mice. Applying GSEA to both mouse and human samples revealed upregulation of 92 gene sets in MWCNT mice and 142 gene sets in sarcoidosis patients. Commonly activated pathways in both MWCNT mice and sarcoidosis included adaptive immunity, T-cell signaling, IL-12/IL-17 signaling, and oxidative phosphorylation. Differences in gene set enrichment between MWCNT mice and sarcoidosis patients were also observed. We applied network analysis to differentially expressed genes common between the MWCNT model and sarcoidosis to identify key drivers of disease. In conclusion, an integrated network and transcriptomics approach revealed substantial functional similarities between a murine model and human sarcoidosis particularly with respect to activation of immune-specific pathways.

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Section: Discussionmentioning

confidence: 99%

Transcriptional survey of alveolar macrophages in a murine model of chronic granulomatous inflammation reveals common themes with human sarcoidosis

Mohan

Malur

McPeek

et al. 2018

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Herndon et al's model of urease coupled to microbeads induced sarcoidosis-like granulomas in rats suggesting that urease alone is insufficient to trigger disease. They identified a potential role of urease in granuloma formation (15). However, a commonly accepted animal model of sarcoidosis is lacking.…”

Section: Discussionmentioning

confidence: 99%

IL-17A Can Promote Propionibacterium acnes-Induced Sarcoidosis-Like Granulomatosis in Mice

Song

Zhao

et al. 2019

Front. Immunol.

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The etiology of sarcoidosis is unknown. In this study, Propionibacterium acnes (PA) was used to induce sarcoidosis-like granulomatous inflammation in a mouse model. Wild-Type (WT) C57BL/6 mice were divided into three groups: (1) WT-PA group; (2) WT-PA + Incomplete Freund's Adjuvant (IFA) group; and (3) WT-PBS group. Loose granuloma formation was observed in the lungs on day 56 in the WT-PA and WT-PA + IFA groups. The proportions of peripheral Th17 cells in the WT-PA ( p = 0.0004) and WT-PA + IFA groups ( p = 0.0005) were significantly higher than that in the WT-PBS group. The proportions of peripheral Treg cells in the WT-PA ( p < 0.0001) and WT-PA + IFA groups ( p < 0.0001) were lower than that in the WT-PBS group. Then, to explore the mechanism of IL-17, Wild-Type (WT) C57BL/6 mice were divided into three groups: (1) WT-PBS group (2) WT-PA group; (3) WT-PA + mouse IL-17A neutralizing antibody (IL-17Ab) group. IL-17A gene knockout mice (KO) were divided into two groups: (1) KO -PA group; (2) KO-PBS group. The KO-PA and WT-PA + IL-17Ab groups showed reduced inflammation and no loose granuloma formation on day 56. As compared to the WT-PA group, the ratio of peripheral Th17 in the KO-PA ( p < 0.0001) and WT-PA + IL-17Ab groups ( p < 0.0001) decreased, while the ratio of peripheral Treg in the KO-PA ( p < 0.0001) and WT-PA + IL-17Ab ( p = 0.0069) groups increased on day 56. Hence, PA can be used to establish a mouse model of sarcoidosis-like granuloma. IL-17A plays an important role in experimental sarcoidosis-like granuloma formation.

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“…Carbon nanotube induced granulomatous lung disease has been demonstrated in an animal model and has shown several similarities to sarcoidosis (121,122). Numerous components of infectious agents, particularly mycobacteria and Propionibacterium acnes have mimicked features of sarcoidosis in animal models (123)(124)(125)(126). These models have demonstrated similar immune responses in terms of T-cell function and the production of cytokines seen in sarcoidosis (120).…”

Section: Animal and Experimental Models Of Granulomatous Diseasementioning

confidence: 99%

Environmental Risk Factors for Sarcoidosis

Judson

2020

Front. Immunol.

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Sarcoidosis is a multisystem granulomatous disease that may affect any body organ. Sarcoidosis is associated with many environmental and occupational exposures. Because the exact immunopathogenesis of sarcoidosis is unknown, it is not known whether these exposures are truly causing sarcoidosis, rendering the immune system more susceptible to the development of sarcoidosis, exacerbating subclinical cases of sarcoidosis, or causing a granulomatous condition distinct from sarcoidosis. This manuscript outlines what is known about the immunopathogenesis of sarcoidosis and postulates mechanisms whereby these exposures could cause or exacerbate the disease. We also describe the varied environmental and occupational exposures that have been associated with sarcoidosis. This includes potential infectious exposures such as mycobacteria and Propionibacterium acnes, a skin commensal bacterium, as well as non-infectious environmental exposures including inhaled bioaerosols, metal dusts and products of combustion. Further insights concerning the relationship of environmental exposures to the development of sarcoidosis may have a major impact on the prevention and treatment of this enigmatic disease.

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Urease and Helicobacter spp. Antigens in Pulmonary Granuloma

Cited by 10 publications

References 40 publications

Transcriptional survey of alveolar macrophages in a murine model of chronic granulomatous inflammation reveals common themes with human sarcoidosis

Transcriptional survey of alveolar macrophages in a murine model of chronic granulomatous inflammation reveals common themes with human sarcoidosis

IL-17A Can Promote Propionibacterium acnes-Induced Sarcoidosis-Like Granulomatosis in Mice

Environmental Risk Factors for Sarcoidosis

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