Development of a Sarcoidosis Murine Lung Granuloma Model Using<i>Mycobacterium</i>Superoxide Dismutase A Peptide

Swaisgood, Carmen M.; Oswald-Richter, Kyra; Moeller, Stephen D.; J, Klemenc; Ruple, Lisa; Farver, Carol; Drake, John M.; Culver, Daniel A.; Drake, Wonder

doi:10.1165/rcmb.2009-0350oc

Cited by 42 publications

(30 citation statements)

References 24 publications

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“…Interestingly, measurement of serum amyloid has been found to correlate with disease activity in pulmonary sarcoidosis (33). The recent development of antigenspecific rodent models of granuloma formation should facilitate further unraveling of the responsible mechanisms (32,34).…”

Section: Etiology and Pathogenesismentioning

confidence: 99%

A Concise Review of Pulmonary Sarcoidosis

Baughman

Culver²,

Judson

2011

Am J Respir Crit Care Med

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432

330

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This is an update on sarcoidosis, focusing on etiology, diagnosis, and treatment. In the area of etiopathogenesis, we now have a better understanding of the immune response that leads to the disease as well as genetic factors that modify both the risk for the disease and its clinical outcome. Several groups have also identified possible agents as a cause for sarcoidosis. Although none of these potential causes has been definitely confirmed, there is increasing evidence to support that one or more infectious agents may cause sarcoidosis, although this organism may no longer be viable in the patient. The diagnosis of sarcoidosis has been significantly aided by new technology. This includes the endobronchial ultrasound, which has been shown to increase the yield of needle aspiration of mediastinal and hilar lymph nodes. The positive emission tomography scan has proven useful for selecting possible biopsy sites by identifying organ involvement not appreciated by routine methodology. It has also helped in assessing cardiac involvement. The biologic agents, such as the anti-tumor necrosis factor antibodies, have changed the approach to refractory sarcoidosis. There is increasing evidence that the clinician can identify which patient is most likely to benefit from such therapy. As new and more potent antiinflammatory agents have been developed, it is clear that there are other factors that burden the patient with sarcoidosis, including fatigue and sarcoidosis-associated pulmonary hypertension. There have been several recent studies demonstrating treatment options for these problems.

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Section: Etiology and Pathogenesismentioning

confidence: 99%

A Concise Review of Pulmonary Sarcoidosis

Baughman

Culver²,

Judson

2011

Am J Respir Crit Care Med

Self Cite

432

330

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“…Some granuloma-producing animal models of sarcoidosis using different bacteria and bacterial products have been proposed; however, there is yet to be a consensus on the ideal animal model (6)(7)(8)(9). The anaerobic gram-positive P. acnes is the strongest bacterial candidate for a causative agent of sarcoidosis (10) because it is the only bacterium to be cultured from sarcoidosis lesions (2) and it has been localized within sarcoidosis granulomas (3).…”

Section: Clinical Relevancementioning

confidence: 99%

Induction of Pulmonary Granuloma Formation byPropionibacterium acnesIs Regulated by MyD88 and Nox2

Werner

Escolero

Hewlett

et al. 2017

Am J Respir Cell Mol Biol

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Sarcoidosis is characterized by noncaseating granulomas with an unknown cause that present primarily in the lung. Propionibacterium acnes, an immunogenic commensal skin bacterium involved in acne vulgaris, has been implicated as a possible causative agent of sarcoidosis. Here, we demonstrate that a viable strain of P. acnes isolated from a patient with sarcoidosis and instilled intratracheally into wild-type mice can generate pulmonary granulomas similar to those observed in patients with sarcoidosis. The formation of these granulomas is dependent on the administration of viable P. acnes. We also found that mice deficient in the innate immunity adapter protein MyD88 had a greater number and a larger area of granuloma lesions compared with wild-type mice administered P. acnes. Early after P. acnes administration, wild-type mice produced proinflammatory mediators and recruited neutrophils into the lung, a response that is dependent on MyD88. In addition, there was an increase in granuloma number and size after instillation with P. acnes in mice deficient in CybB, a critical component of nicotinamide adenine dinucleotide phosphate oxidase required for the production of reactive oxygen species in the phagosome. Myd882/2 or Cybb 2/2 mice both had increased persistence of P. acnes in the lung, together with enhanced granuloma formation. In conclusion, we have generated a mouse model of early granuloma formation induced by a clinically relevant strain of P. acnes isolated from a patient with sarcoidosis, and, using this model, we have shown that a deficiency in MyD88 or CybB is associated with impaired bacterial clearance and increased granuloma formation in the lung.

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“…11 Animal models of disseminated granulomatous disease have also been generated using these antigens. 12 One difficulty with these studies is that only a subset of sarcoidosis patients demonstrates antibodies to either of these agents. This could mean that there is more than one cause of sarcoidosis.…”

Section: Etiology and Genetics Of Sarcoidosismentioning

confidence: 99%

Neuro-ophthalmic sarcoidosis

Baughman¹,

Weiss²,

Golnik³

2012

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Neuro-ophthalmic disease occurs in about a third of patients with neurosarcoidosis. Optic nerve involvement is the most common manifestation, but other cranial nerves and the optic chiasm can be involved. However, there are several other common diseases that cause optic neuropathy, including multiple sclerosis. The diagnosis of sarcoidosis can often be made based on the multi-organ nature of the disease and ancillary testing. Most patients with neuro-ophthalmic sarcoidosis require systemic therapy. While corticosteroids are usually the first step in therapy, cytotoxic agents such as methotrexate and azathioprine have been useful as steroid-sparing agents for chronic disease. The monoclonal antibodies directed against tumor necrosis factor have been reported as effective in refractory cases of neuro-ophthalmic disease.

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Development of a Sarcoidosis Murine Lung Granuloma Model UsingMycobacteriumSuperoxide Dismutase A Peptide

Cited by 42 publications

References 24 publications

A Concise Review of Pulmonary Sarcoidosis

A Concise Review of Pulmonary Sarcoidosis

Induction of Pulmonary Granuloma Formation byPropionibacterium acnesIs Regulated by MyD88 and Nox2

Neuro-ophthalmic sarcoidosis

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