Takes your breath away – the immunology of allergic alveolitis

McSharry, Charles; Anderson, Kenneth E.; Bourke, Stephen; Boyd, G.

doi:10.1046/j.1365-2249.2002.01849.x

Cited by 63 publications

(36 citation statements)

References 69 publications

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“…Although the precise functions of CD8 ϩ T cells in the development of HP are unknown, it has been suggested that CD8 ϩ T cells and activated macrophages produce MIP-1␣, which induces granuloma formation by facilitating the differentiation of alveolar macrophages into epithelioid cells and multinuclear giant cells (31,43). In addition, IL-8 and MCP-1 are chemotactic for Ag-sensitized CD8 ϩ T cells and, to lesser extent, CD4 ϩ T cells in the lungs (4,44). Therefore, it is conceivable that several chemokines produced by activated macrophages recruit CD8 ϩ T cells into the lung tissues and are activated and proliferate due to the effects of IFN-␥-producing Gr1 ϩ neutrophils, and consequently induce granuloma formation in SR-induced HP, which is regulated by NKT cells.…”

Section: Discussionmentioning

confidence: 99%

IL-4-Secreting NKT Cells Prevent Hypersensitivity Pneumonitis by Suppressing IFN-γ-Producing Neutrophils

Hwang

Kim

Park

et al. 2006

The Journal of Immunology

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Hypersensitivity pneumonitis (HP) is mediated by Th1 immune response. NKT cells regulate immune responses by modulating the Th1/Th2 balance. Therefore, we postulated that NKT cells play a critical role in the development of the HP by modulating the Th1/Th2 response. To address this issue, we explored the functional roles of NKT cells in Saccharopolyspora rectivirgula (SR)-induced HP. In CD1d−/− mice, the HP was worse in terms of histological changes, hydroxyproline levels, the CD4:CD8 ratio in bronchoalveolar lavage fluid, and SR-specific immune responses than in control mice. CD1d−/− mice showed elevated IFN-γ production in the lung during the HP, and this was produced mainly by Gr-1+ neutrophils. The blockade of IFN-γ in CD1d−/− mice attenuated the HP, whereas the injection of rIFN-γ aggravated it. Moreover, the depletion of Gr-1+ neutrophils reduced CD8+ T cell numbers in bronchoalveolar lavage fluid during the HP. The adoptive transfer of IL-4−/− mouse NKT cells did not attenuate the HP, whereas wild-type or IFN-γ−/− mouse NKT cells suppressed the HP. In conclusion, NKT cells producing IL-4 play a protective role in SR-induced HP by suppressing IFN-γ-producing neutrophils, which induce the activation and proliferation of CD8+ T cells in the lung.

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Section: Discussionmentioning

confidence: 99%

IL-4-Secreting NKT Cells Prevent Hypersensitivity Pneumonitis by Suppressing IFN-γ-Producing Neutrophils

Hwang

Kim

Park

et al. 2006

The Journal of Immunology

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“…The inflammatory process in the acute phase of HP characteristically features a nonatopic neutrophilic inflammation of the respiratory bronchioles, alveoli, and interstitial tissue of the lungs. [45][46][47][48] Similarly to asthma, the pathology is induced by repeated exposure to airborne agents in individuals previously sensitized to specific agents via the pulmonary mucosa, and manifests itself in acute, subacute, or chronic forms. 48,49 However, in contrast to asthma, the causative agents are small organic particles, often of microbial origin, or volatile reactive chemicals, and the resulting pathology is clearly of a different nature.…”

Section: Understanding Asthma Through Its Counterpart-hypersensitivitmentioning

confidence: 99%

Where Asthma and Hypersensitivity Pneumonitis Meet and Differ

Bogaert

Tournoy

Naessens

et al. 2009

The American Journal of Pathology

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Asthma is a type-I allergic airway disease characterized by Th 2 cells and IgE. Episodes of bronchial inflammation, eosinophilic in nature and promoting bronchoconstriction, may become chronic and lead to persistent respiratory symptoms and irreversible structural airway changes. Representative mostly of mild to moderate asthma, this clinical definition fails to account for the atypical and often more severe phenotype found in a considerable proportion of asthmatics who have increased neutrophil cell counts in the airways as a distinguishing trait. Neutrophilic inflammation is a hallmark of another type of allergic airway pathology , hypersensitivity pneumonitis. Considered as an immune counterpart of asthma, hypersensitivity pneumonitis is a prototypical type-III allergic inflammatory reaction involving the alveoli and lung interstitium, steered by Th 1 cells and IgG and, in its chronic form, accompanied by fibrosis. Although pathologically very different and commonly approached as separate disorders, as discussed in this review, clinical studies as well as data from animal models reveal undeniable parallels between both airway diseases. Danger signaling elicited by the allergenic agent or by accompanying microbial patterns emerges as critical in enabling immune sensitization and in determining the type of sensitization and ensuing allergic disease. On this basis , we propose that asthma allergens cause severe noneosinophilic asthma because of sensitization in the presence of hypersensitivity pneumonitis-promoting danger signaling.

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“…HP is considered a T H 1-driven disease and Type IV delayed hypersensitivity is a hallmark of subacute and chronic forms of HP. Although still a matter of debate, it has often been suggested that Type III immune complex-driven hypersensitivity responses account for the early stage of acute HP (Kaltreider 1993;McSharry et al 2002). In support of this, the majority of patients have precipitating antibodies that are specific for the offending antigen (Reboux et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Early immunopathological events in acute model of mycobacterial hypersensitivity pneumonitis in mice

Johansson

Boivin

Yadav

2017

Journal of Immunotoxicology

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Prolonged exposure to antigens of non-tuberculous mycobacteria species colonizing industrial metalworking fluid (MWF), particularly Mycobacterium immunogenum (MI), has been implicated in chronic forms of hypersensitivity pneumonitis (HP) in machinists based on epidemiology studies and long-term exposure of mouse models. However, a role of short-term acute exposure to these antigens has not been described in the context of acute forms of HP. This study investigated short-term acute exposure of mice to MI cell lysate (or live cell suspension) via oropharyngeal aspiration. The results showed there was a dose-and timedependent increase (peaking at 2 h post-instillation) in lung immunological responses in terms of the pro-(TNFa, IL-6, IL-1b) and anti-inflammatory (IL-10) cytokines. Bronchoalveolar lavage and histology showed neutrophils as the predominant infiltrating cell type, with lymphocytes <5% at all timepoints or concentrations. Granulomatous inflammation peaked between 8 and 24 h post-exposure, and resolved by 96 h. Live bacterial challenge, typically encountered in real-world exposures, showed no significant differences from bacterial lysate except for induction of appreciable levels of interferon (IFN)-c, implying additional immunogenic potential. Collectively, the short-term mycobacterial challenge in mice led to a transient early immunopathologic response, with little adaptive immunity, which is consistent with events associated with human acute forms of HP. Screening of MWF-originated mycobacterial genotypes/variants (six of MI, four of M. chelonae, two of M. abscessus) showed both inter-and intra-species differences, with MI genotype MJY10 being the most immunogenic. In conclusion, this study characterized the first short-term mycobacterial exposure mouse model that mimics acute HP in machinists; this could serve as a potentially useful model for rapid screening of field MWF-associated mycobacteria for routine and timely occupational risk assessment and for investigating early biomarkers and mechanisms of this understudied immune lung disease. ARTICLE HISTORY

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Takes your breath away – the immunology of allergic alveolitis

Cited by 63 publications

References 69 publications

IL-4-Secreting NKT Cells Prevent Hypersensitivity Pneumonitis by Suppressing IFN-γ-Producing Neutrophils

IL-4-Secreting NKT Cells Prevent Hypersensitivity Pneumonitis by Suppressing IFN-γ-Producing Neutrophils

Where Asthma and Hypersensitivity Pneumonitis Meet and Differ

Early immunopathological events in acute model of mycobacterial hypersensitivity pneumonitis in mice

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