The genetic heterogeneity of mendelian susceptibility to mycobacterial diseases

Al‐Muhsen, Saleh; Casanova, Jean‐Laurent

doi:10.1016/j.jaci.2008.10.037

Cited by 214 publications

(185 citation statements)

References 102 publications

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“…Indeed, even infected immune-competent human beings or animals have hardly ever been observed to eliminate the mycobacteria, resulting in a high incidence of latent infection and the reactivation of disease when the immune system is weakened. 20,21 Together, the emerging evidence supports the contemporary view that the granuloma represents a symbiotic tissue microenvironment for the mutual benefit of both the host and the mycobacterium. However, whether the mycobacterial granuloma is indeed an immunologically suppressed microenvironment remains largely to be established, and the underlying mechanisms are still unclear.…”

mentioning

confidence: 67%

Pulmonary Mycobacterial Granuloma

Shaler

Kugathasan

McCormick

et al. 2011

The American Journal of Pathology

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The granuloma, a hallmark of host defense against pulmonary mycobacterial infection, has long been believed to be an active type 1 immune environment. However, the mechanisms regarding why granuloma fails to eliminate mycobacteria even in immune-competent hosts, have remained largely unclear. By using a model of pulmonary Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection, we have addressed this issue by comparing the immune responses within the airway luminal and granuloma compartments. We found that despite having a similar immune cellular profile to that in the airway lumen, the granuloma displayed severely suppressed type 1 immune cytokine but enhanced chemokine responses. Both antigen-presenting cells (APCs) and T cells in granuloma produced fewer type 1 immune molecules including tumor necrosis factor-␣ (TNF-␣), interferon-␥ (IFN-␥), and nitric oxide. As a result, the granuloma APCs developed a reduced capacity to phagocytose mycobacteria and to induce T-cell proliferation. To examine the molecular mechanisms, we compared the levels of immune suppressive cytokine IL-10 in the airway lumen and granuloma and found that both granuloma APCs and T cells produced much more IL-10. Thus, IL-10 deficiency restored type 1 immune activation within the granuloma while having a minimal effect within the airway lumen. Hence, our study provides the first experimental evidence that, contrary to the conventional belief, the BCG-induced lung granuloma represents a symbiotic host-microbe microenvironment characterized by suppressed type 1 immune activation.

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confidence: 67%

Pulmonary Mycobacterial Granuloma

Shaler

Kugathasan

McCormick

et al. 2011

The American Journal of Pathology

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“…[5][6][7][8] Risk factors for nontuberculous mycobacterial disease include defects in the host immune response due to inherited or acquired conditions, particularly those that affect the Th1 cell and macrophage pathways, and exposure to environmental NTMs; repeated surgical interventions in the genitourinary tract could also introduce environmental MAC. 9 There was no evidence that our patient had any recognized risk factors for MAC infection, nor any signs of being immune-compromised.…”

Section: Discussionmentioning

confidence: 74%

Urinary mycobacterium avium presenting as sterile pyuria

Yang

Samplaski

Mazzulli

et al. 2016

CUAJ

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A 65-year-old healthy woman presented with persistent, asymptomatic sterile pyuria detected by her family physician. While she did not have symptoms, the patient recounts that she has had cloudy urine for years. Cultures of the urine for bacteria showed no growth and no fungi were identified. First-morning urine samples were sent for both tuberculosis and nontuberculosis mycobacterium species testing. The culture grew genotypically identified Mycobaterium avium complex (MAC). Mantoux skin testing was positive. No urological abnormalities were detected by ultrasound and computed tomography (CT) imaging of the urinary tract. IntroductionMAC is classified as a slow-growing nontuberculous mycobacterium (NTM).1 While MAC is ubiquitous in the environment and is the most common disease-causing NTM in humans, there are very few reported cases of MAC infection in the urine and only two reported cases of asymptomatic MAC urine infection. Predisposing factors for NTM infections include defects in host immunity and direct exposure to the NTMs. MAC is ubiquitous in the soil, so those working with soil may be at higher risk of MAC infections.The diagnosis of a MAC urine infection is made with urine culture for MAC and/or polymerase chain reaction (PCR). Direct staining for acid-fast bacilli is considered unreliable. For most patients with a MAC infection, skin Mantoux testing is positive.Testing for MAC infection should be considered for patients with sterile pyuria. While MAC urine infections are not commonly reported, this may reflect how commonly testing for MAC infection is performed rather than how commonly MAC infection occurs. Case reportA 65-year-old woman presented to general urology clinic with persistent, asymptomatic sterile pyuria. This was detected incidentally on routine urinalysis performed by her primary care physician. However, on further questioning, she reported having had cloudy urine for years. Several urinalyses performed by her primary care physician demonstrated abundant neutrophils, but cultures for bacteria and fungus showed no growth and microscopic examination for parasites was negative. She denied any history of dysuria, hematuria, fevers, chills, or other systemic complaints.The patient had a relatively unremarkable medical history with the only medical issues being psoriasis, hypertension, and hypercholesterolemia. She was born in the Czech Republic and emmigrated to Canada at 20 years of age. There was no family history of tuberculosis. She had no antecedent travel or exposure to sick individuals. The patient's physical examination was unremarkable and her repeated urinalyses showed 5-10 leukocytes per high-powered field on urine microscopy. This urine sample again demonstrated no growth on routine culture. Due to the patient's history of repeated sterile pyuria, a first-morning urine was sent for culture for Mycobaterium tuberculosis, Mycobaterium avium, fungus, and examination for parasites. The culture grew genotypically identified Mycobaterium avium complex (MAC).Mantoux skin test ...

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“…They are also very sensitive to the infection with Salmonella sp. and with other intracellular bacteria and fungi [14].…”

Section: Factors Influencing Susceptibility To Tb Infectionmentioning

confidence: 99%

What Factors May Influence Epidemiological Situation of Tuberculosis in Poland and in the World?

Rowińska-Zakrzewska¹,

Korzeniewska-Koseła²,

Augustynowicz–Kopeć³

et al. 2016

Advances in Respiratory Medicine

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The authors present the review of factors influencing epidemiological situation of tuberculosis in Poland and in the world. The groups of increased risk of tuberculosis, and clinical conditions predisposing to activation of latent tuberculosis infection (LTBI) such as HIV, uremia, diabetes mellitus, transplantation of organs, treatment with glucocorticosteroids and with antibodies to TNF and to its receptors, were presented. The higher prevalence and worse prognosis of tuberculosis in elderly people was emphasised. The methods of LTBI recognition, according to recent recommendations, with special consideration to patients in immunosupression, were shown. Methods of treatment to prevent LTBI activation, according to WHO experts, were also presented. All data were discussed in relation to the actual epidemiological situation of tuberculosis in Poland.

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The genetic heterogeneity of mendelian susceptibility to mycobacterial diseases

Cited by 214 publications

References 102 publications

Pulmonary Mycobacterial Granuloma

Pulmonary Mycobacterial Granuloma

Urinary mycobacterium avium presenting as sterile pyuria

What Factors May Influence Epidemiological Situation of Tuberculosis in Poland and in the World?

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