Rapid Detection and Immune Characterization of Mycobacterium abscessus Infection in Cystic Fibrosis Patients

Steindor, Mathis; Nkwouano, Vanesa; Mayatepek, Ertan; MacKenzie, Colin R.; Schramm, Dirk; Jacobsen, Marc

doi:10.1371/journal.pone.0119737

Cited by 18 publications

(9 citation statements)

References 26 publications

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“…Similarly, mice or guinea pigs infected with aerosolized MAB exhibit an early influx of IFN-γ+ T cells preceding successful clearance (48). Further studies have shown that depletion of CD4 T cells or neutralization of IFN-γ causes worsening of MAC and MAB infection in mice (49–51). Control of MAC and MAB infection also requires other key cytokines such as TNF-α and IL-12 (49, 52–54).…”

Section: Discussionmentioning

confidence: 99%

BCG Vaccination Induces M. avium and M. abscessus Cross-Protective Immunity

et al. 2019

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Pulmonary non-tuberculous mycobacterial (NTM) infections particularly caused by Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MAB) are becoming major health problems in the U.S. New therapies or vaccines which will help prevent the disease, shorten treatment duration and/or increase treatment success rates are urgently needed. This study was conducted with the objective of testing the hypothesis that Bacillus Calmette Guerin (BCG), a vaccine used for prevention of serious forms of tuberculosis (TB) in children and adolescents in tuberculosis hyperendemic countries, induces cross-protective T cell immunity against Mycobacterium avium (MAV) and MAB. Human TB and NTM cross-protective T cells were quantified using flow cytometric assays. The ability of BCG expanded T cells to inhibit the intracellular growth of MAV and MAB was assessed in co-cultures with infected autologous macrophages. In both BCG-vaccinated and M. tuberculosis (Mtb)-infected mice, NTM cross-reactive immunity was measured using IFN-γ ELISPOT assays. Our results demonstrate the following key findings: (i) peripheral blood mononuclear cells from TB skin test-positive individuals contain MAV and MAB cross-reactive T cells, (ii) both BCG vaccination and Mtb infection of mice induce MAV and MAB cross-reactive splenic cells, (iii) BCG-expanded T cells inhibit intracellular MAV and MAB, (iv) CD4, CD8, and γδ T cells play important roles in inhibition of intracellular MAV and MAB and (v) BCG vaccination of healthy volunteers induces TB and NTM cross-reactive T cells. In conclusion, BCG-vaccination induces NTM cross-reactive immunity, and has the potential for use as a vaccine or immunotherapy to prevent and/or treat pulmonary NTM disease.

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Section: Discussionmentioning

confidence: 99%

BCG Vaccination Induces M. avium and M. abscessus Cross-Protective Immunity

et al. 2019

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“…Here, we dissect faults in immunity in two cohorts of patients (CF and elderly) with NTM lung infection and matched controls to identify the underlying blood immune signatures of each disease. Blood was examined given: (i) T cells are known to traffic between the blood and lung ( 36 ); (ii) NTM-specific T cells have been observed in the blood ( 37 ); and (iii) blood is easy to access for diagnostic tests. The first cohort included CF patients with active NTM disease, CF patients with past NTM disease who had been successfully treated and were now in disease remission, CF patients with chronic Pa infection who had no history of NTM infection and a group of matched healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Anomalies in T Cell Function Are Associated With Individuals at Risk of Mycobacterium abscessus Complex Infection

et al. 2018

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The increasing global incidence and prevalence of non-tuberculous mycobacteria (NTM) infection is of growing concern. New evidence of person-to-person transmission of multidrug-resistant NTM adds to the global concern. The reason why certain individuals are at risk of NTM infections is unknown. Using high definition flow cytometry, we studied the immune profiles of two groups that are at risk of Mycobacterium abscessus complex infection and matched controls. The first group was cystic fibrosis (CF) patients and the second group was elderly individuals. CF individuals with active M. abscessus complex infection or a history of M. abscessus complex infection exhibited a unique surface T cell phenotype with a marked global deficiency in TNFα production during mitogen stimulation. Importantly, immune-based signatures were identified that appeared to predict at baseline the subset of CF individuals who were at risk of M. abscessus complex infection. In contrast, elderly individuals with M. abscessus complex infection exhibited a separate T cell phenotype underlined by the presence of exhaustion markers and dysregulation in type 1 cytokine release during mitogen stimulation. Collectively, these data suggest an association between T cell signatures and individuals at risk of M. abscessus complex infection, however, validation of these immune anomalies as robust biomarkers will require analysis on larger patient cohorts.

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“…Reduced Th1 and Th2 cell immune responses associated with upregulated Th17 response have been reported in patients with MAbsC pulmonary disease compared to healthy controls [26]. In a small study of CF patients, an increased frequency of antigen-specific peripheral blood T cells expressing CD40L(+) but not IL-2(−) was found mostly in patients with MAbsC pulmonary disease [27]. This limited immune profiling information suggests that MAbsC infections are associated with alterations in some specific pathways of cell-mediated immunity that may contribute to disease progression.…”

Section: Risk Factorsmentioning

confidence: 99%

Mycobacterium abscessus disease in lung transplant recipients: Diagnosis and management

Chandrashekaran

Escalante

Kennedy

2017

Journal of Clinical Tuberculosis and Other Mycobacterial Diseas

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Mycobacterium abscessus complex (MAbsC ) disease in lung transplant recipients is increasingly being recognized as an important cause of graft function decline and suboptimal outcomes. Lung transplant recipients appear to be at the highest risk of MAbsC among solid organ transplant recipients, as they have more intense immunosuppression, and the organisms preferentially inhabit the lungs. MAbsC is the most resistant species of rapidly growing mycobacteria and difficult to treat, causing considerable mortality and morbidity in immunocompetent and immunosuppressed patients. Herein we describe the risk factors, epidemiology, clinical features, diagnostics, and treatment strategies of MAbsC in lung transplant recipients.

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Rapid Detection and Immune Characterization of Mycobacterium abscessus Infection in Cystic Fibrosis Patients

Cited by 18 publications

References 26 publications

BCG Vaccination Induces M. avium and M. abscessus Cross-Protective Immunity

BCG Vaccination Induces M. avium and M. abscessus Cross-Protective Immunity

Anomalies in T Cell Function Are Associated With Individuals at Risk of Mycobacterium abscessus Complex Infection

Mycobacterium abscessus disease in lung transplant recipients: Diagnosis and management

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