Cigarette Smoking Impairs Human Pulmonary Immunity to <i>Mycobacterium tuberculosis</i>

O’Leary, Seónadh M.; Coleman, Michelle; Chew, Wui Mei; Morrow, Colette; McLaughlin, Anne Marie; Gleeson, Laura E.; O’Sullivan, Mary P.; Keane, Joseph

doi:10.1164/rccm.201407-1385oc

Cited by 116 publications

(127 citation statements)

References 44 publications

(61 reference statements)

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“…Human AM were retrieved at bronchoscopy after informed consent, as approved by the Research Ethics Committee of St. James's Hospital (Dublin, Ireland), and prepared and cultured as previously reported (8,9). Cells were cultured for 24 h prior to experimentation.…”

Section: Cell Culturementioning

confidence: 99%

“…M. tuberculosis strain H37Rv, gamma-irradiated whole cells, NR-49098 (BEI Resources, National Institute of Allergy and Infectious Diseases, National Institutes of Health) was prepared according to the supplier's instructions. Bacteria were resuspended, and multiplicity of infection (MOI) was determined for each donor as previously described (8,9). Cells were infected at MOI 1-5 bacilli/cell for 3 h, extracellular bacteria were removed, and fresh media were applied to allow incubation for specified times.…”

Section: Cell Culturementioning

confidence: 99%

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Cutting Edge: Mycobacterium tuberculosis Induces Aerobic Glycolysis in Human Alveolar Macrophages That Is Required for Control of Intracellular Bacillary Replication

Gleeson

Sheedy

Pålsson-McDermott

et al. 2016

The Journal of Immunology

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Recent advances in immunometabolism link metabolic changes in stimulated macrophages to production of IL-1β, a crucial cytokine in the innate immune response to Mycobacterium tuberculosis. To investigate this pathway in the host response to M. tuberculosis, we performed metabolic and functional studies on human alveolar macrophages, human monocyte-derived macrophages, and murine bone marrow–derived macrophages following infection with the bacillus in vitro. M. tuberculosis infection induced a shift from oxidative phosphorylation to aerobic glycolysis in macrophages. Inhibition of this shift resulted in decreased levels of proinflammatory IL-1β and decreased transcription of PTGS2, increased levels of anti-inflammatory IL-10, and increased intracellular bacillary survival. Blockade or absence of IL-1R negated the impact of aerobic glycolysis on intracellular bacillary survival, demonstrating that infection-induced glycolysis limits M. tuberculosis survival in macrophages through induction of IL-1β. Drugs that manipulate host metabolism may be exploited as adjuvants for future therapeutic and vaccination strategies.

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Section: Cell Culturementioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

Cutting Edge: Mycobacterium tuberculosis Induces Aerobic Glycolysis in Human Alveolar Macrophages That Is Required for Control of Intracellular Bacillary Replication

Gleeson

Sheedy

Pålsson-McDermott

et al. 2016

The Journal of Immunology

Self Cite

245

288

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“…Prolonged exposure to the cytotoxic and pro-inflammatory agents in cigarette smoke results in chronic inflammation, oxidative stress and immunosuppression, increasing susceptibility to respiratory infection, particularly with the bacterial pathogens, Streptococcus pneumoniae and Mycobacterium tuberculosis [45]. Notwithstanding suppression of pulmonary host defences [48], smoking also poses the risk of damage to lung epithelium and endothelium, facilitating extrapulmonary dissemination of microbial pathogens and possibly entry of HIV [49,50].…”

Section: Smoking and Immunitymentioning

confidence: 99%

Impact of HIV infection and smoking on lung immunity and related disorders

2015

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HIV-infected persons not only have higher rates of smoking than the general population, but are also unusually vulnerable to the associated adverse health effects, both infective and noninfective in origin. Indeed, in the setting of well-organised care and availability of highly active antiretroviral therapy, HIV-infected smokers lose more life-years to smoking than to HIV infection per se, presenting a major challenge to healthcare providers. Not surprisingly, the respiratory system is particularly susceptible to the damaging interactive chronic inflammatory and immunosuppressive effects of HIV and smoking, intensifying the risk of the development of opportunistic infections, as well as lung cancer and obstructive lung disorders. The impact of smoking on the immunopathogenesis and frequencies of these respiratory conditions in the setting of HIV infection, as well as on the efficacy of antiretroviral therapy, represent the primary focus of this review. @ERSpublications Smoking exacerbates the immunosuppressive/pro-inflammatory effects of HIV, increasing the risk of pulmonary disease

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“…Preexisting lung disease (e.g., heavy smoking, chronic obstructive pulmonary disease) is the most prevalent underlying condition among patients with pulmonary M. kansasii infections (34). Underlying lung conditions likely increase susceptibility to infection due to impaired alveolar macrophage phagocytic activity (35) and immune responses (36). However, the lack of association between underlying lung disease alone and disseminated M. kansasii disease (34) suggests that extrapulmonary immune responses largely remain intact in these patients.…”

Section: Discussionmentioning

confidence: 99%

Mediastinal and Disseminated Mycobacterium kansasii Disease in GATA2 Deficiency

et al. 2016

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Rationale: Mycobacterium kansasii usually causes chronic pulmonary infections in immunocompetent patients. In contrast, disseminated M. kansasii disease is commonly associated with advanced human immunodeficiency virus infection, but is reported infrequently in other immunocompromised patients.Objectives: To identify common clinical manifestations and potential risk factors for M. kansasii infection in patients with GATA2 deficiency.Methods: We reviewed M. kansasii disease associated with GATA2 deficiency at one institution and disease associated with primary and other immunodeficiencies reported in the literature. Measurements and Main Results:Nine patients with GATA2 deficiency developed M. kansasii infections. Six patients developed disseminated disease. All patients presented with significant mediastinal lymphadenopathy or abscesses. Seven patients had pulmonary risk factors, including six smokers. The majority of patients had low numbers of neutrophils, monocytes, B cells, CD4 1 T cells, and natural killer cells. Other conditions associated with disseminated M. kansasii disease were thymic disorders and IFN-g/IL-12 defects.Conclusions: Disseminated M. kansasii disease involving mediastinal lymph nodes is surprisingly common in GATA2 deficiency, but also occurs in defects of IFN-g synthesis and response. Disseminated M. kansasii should be considered a marker indicating a need to evaluate for immunodeficiency syndromes.

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Cigarette Smoking Impairs Human Pulmonary Immunity to Mycobacterium tuberculosis

Abstract: In smokers, the pulmonary compartment has a number of macrophage-specific immune impairments that provide some mechanistic explanations whereby cigarette smoking renders a patient susceptible to tuberculosis infection and disease.

Cited by 116 publications

References 44 publications

Cutting Edge: Mycobacterium tuberculosis Induces Aerobic Glycolysis in Human Alveolar Macrophages That Is Required for Control of Intracellular Bacillary Replication

Cutting Edge: Mycobacterium tuberculosis Induces Aerobic Glycolysis in Human Alveolar Macrophages That Is Required for Control of Intracellular Bacillary Replication

Impact of HIV infection and smoking on lung immunity and related disorders

Mediastinal and Disseminated Mycobacterium kansasii Disease in GATA2 Deficiency

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