A TNF-Regulated Recombinatorial Macrophage Immune Receptor Implicated in Granuloma Formation in Tuberculosis

Beham, A.; Püellmann, Kerstin; Laird, Rebecca; Fuchs, Tina; Streich, R; Breysach, Caroline; Roggenbuck, Dirk; Oniga, Septimia; Peccerella, Teresa; Findeisen, Peter; Kzhyshkowska, Julia; Gratchev, Alexei; Schweyer, Stefan; Saunders, Bernadette M.; Wessels, Johannes T.; Möbius, Wiebke; Keane, Joseph; Becker, H.; Ganser, Arnold; Neumaier, Michael; Kaminski, Wolfgang E.

doi:10.1371/journal.ppat.1002375

Cited by 66 publications

(78 citation statements)

References 28 publications

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“…It is noteworthy that combined percentages for renin expression in T-cells and macrophages exceeds 100%. This is probably attributable to the expression of TCRα/β by small numbers of macrophages 5 . Mast cells are an important source of the ANGI-cleaving protease, chymase, but lacked other RAS components.…”

Section: Discussionmentioning

confidence: 99%

A Local Inflammatory Renin-Angiotensin System Drives Sensory Axon Sprouting in Provoked Vestibulodynia

Liao

Chakrabarty

et al. 2017

The Journal of Pain

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Vestibulodynia is a form of provoked vulvodynia characterized by profound tenderness, hyperinnervation, and frequently inflammation within well-defined areas of the human vestibule. Prior experiments in animal models show that inflammatory hypersensitivity and hyperinnervation occur in concert with establishment of a local renin-angiotensin system (RAS). Moreover, mechanical hypersensitivity and sensory axon sprouting are prevented by blocking effects of angiotensin II on AT2 receptors. This case-control study assessed whether a RAS contributes to hyperinnervation observed in human vestibulodynia. Vestibular biopsies from asymptomatic controls or patients’ nontender areas showed moderate innervation and small numbers of inflammatory cells. In women with vestibulodynia, tender areas contained increased numbers of mechanoreceptive nociceptor axons, T-cells, macrophages and B-cells, while mast cells were unchanged. RAS proteins were increased due to greater numbers of T-cells and B-cells expressing angiotensinogen, and increased renin-expressing T-cells and macrophages. Chymase, which converts angiotensin I to angiotensin II, was present in constant numbers of mast cells. To determine if tender vestibular tissue generates angiotensin II that promotes axon sprouting, we conditioned culture medium with vestibular tissue. Rat sensory neurons cultured in control-conditioned medium showed normal axon outgrowth, while those in tender tissue-conditioned medium showed enhanced sprouting that was prevented by adding an AT2 antagonist or angiotensin II neutralizing antibody. Hypersensitivity in provoked vestibulodynia is therefore characterized by abnormal mechano-nociceptor axon proliferation, which is attributable to inflammatory cell-derived angiotensin II (or a closely related peptide) acting on neuronal AT2 receptors. Accordingly, reducing inflammation or blocking AT2 represent rational strategies to mitigate this common pain syndrome. Perspective: This study provides evidence that local inflammation leads to angiotensin II formation which acts on the angiotensin II receptor type 2 to induce nociceptor axon sprouting in vulvodynia. Preventing inflammation and blocking AT2 therefore present potential pharmacological strategies for reducing vestibular pain.

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Section: Discussionmentioning

confidence: 99%

A Local Inflammatory Renin-Angiotensin System Drives Sensory Axon Sprouting in Provoked Vestibulodynia

Liao

Chakrabarty

et al. 2017

The Journal of Pain

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“…In latency, infection is contained in a non‐dividing state within macrophages, but can become activated if the host immune response is perturbed. TNF is an important regulator of macrophage functions that are required to control infection, and can also contribute to containment of the disease by promoting migration of immune cells and granuloma formation at sites of infection . Further evidence for the role of TNF in tuberculosis is provided by the increased risk of reactivation of Mycobacterium tuberculosis infection seen in patients receiving TNF blockade (see below).…”

Section: The Effects Of Tnf On Bacterial Infectionsmentioning

confidence: 99%

Tumour necrosis factor in infectious disease

Waters

Pober

Bradley

2013

The Journal of Pathology

117

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TNF signals through two distinct receptors, designated TNFR1 and TNFR2, which initiate diverse cellular effects that include cell survival, activation, differentiation, and proliferation and cell death. These cellular responses can promote immunological and inflammatory responses that eradicate infectious agents, but can also lead to local tissue injury at sites of infection and harmful systemic effects. Defining the molecular mechanisms involved in TNF responses, the effects of natural and experimental genetic diversity in TNF signalling and the effects of therapeutic blockade of TNF has increased our understanding of the key role that TNF plays in infectious disease.

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“…Due to the process of calcification of the scars (deposition of calcium from the bloodstream in the scar tissue) the scar tissue and lymph nodes may eventually become hardened, like stone. These scars often appear as round marbles in X-rays and imaging studies and are referred to as a granuloma [18]. If these scars do not show any evidence of calcium on X-ray, they can be difficult to distinguish from cancer.…”

Section: Immune Response Against Tbmentioning

confidence: 99%

Role of Diabetes in prevalence of Tuberculosis

Siddiqui¹

2012

J Diabetes Metab

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Tuberculosis is a lethal disease caused by Mycobacterium tuberculosis. The Mycobacterium initially infects lungs. If the infection spreads beyond the lungs, the symptoms will depend upon the individual organs. Diabetes is a type of metabolic disease in which a person has increased blood sugar level. It's because the body does not produce enough insulin or the cells inside the body do not respond to the insulin that is produced. Diabetics have a three to five time's higher risk of developing tuberculosis (TB) than those without diabetes disease. Diabetes mellitus is an important risk factor for tuberculosis and may affect disease treatment and also the response. Additionally tuberculosis may induce glucose intolerance and worsen the glycaemic control in people with diabetes. The main aim of this Review is to evaluate the epidemiology of diabetes mellitus and tuberculosis disease, the effect of diabetes mellitus on tuberculosis and vice versa.  When the immune system of a patient with dormant TB is weakened, the TB can become active (reactivate) and cause infection in lungs or any other parts of the body. The risk factors for acquiring TB include close-contact situations, alcohol, drug abuse and certain diseases (examples include diabetes, cancer, and HIV) and occupations (for example, health-care workers). The common signs and symptoms of TB include fatigue, fever, weight loss, coughing, and night sweats. The diagnosis of TB involves skin tests, chest X-rays, sputum analysis (smear and culture), and PCR tests to detect the genetic material of the causative bacteria or causative agent [12]. Inactive tuberculosis may be treated with an isoniazid (INH), antibiotic, in order to prevent the TB infection from becoming active. Active TB is usually treated, successfully, with INH in combination with one or more of several drugs, including rifampin (Rifadin), ethambutol (Myambutol), pyrazinamide, and streptomycin [13].

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A TNF-Regulated Recombinatorial Macrophage Immune Receptor Implicated in Granuloma Formation in Tuberculosis

Cited by 66 publications

References 28 publications

A Local Inflammatory Renin-Angiotensin System Drives Sensory Axon Sprouting in Provoked Vestibulodynia

A Local Inflammatory Renin-Angiotensin System Drives Sensory Axon Sprouting in Provoked Vestibulodynia

Tumour necrosis factor in infectious disease

Role of Diabetes in prevalence of Tuberculosis

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