TH1-mediated airway hyperresponsiveness independent of neutrophilic inflammation

Cui, Junqing; Pazdziorko, Stephen; Miyashiro, Joy; Thakker, Paresh; Pelker, Jeffrey W.; DeClercq, Charlene; Jiao, Aiping; Gunn, Jason R.; Mason, Lawrence E.; Leonard, John P.; Williams, Cara; Marušić, Suzana

doi:10.1016/j.jaci.2004.10.046

Cited by 67 publications

(59 citation statements)

References 30 publications

(38 reference statements)

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“…Infection may promote neutrophilic inflammation that is associated with Th1 and IL-17 responses, rather than Th2-dominated, eosinophilic responses, while maintaining some of the clinical features of asthma, such as impaired lung function. Th1 and Th17 responses have been previously shown to be associated with neutrophilic inflammation in mouse models of AAD; however, these studies used adoptive transfer of in vitro polarized Th1 and Th17 cells to demonstrate the link (46,47). In this study, we show that chlamydial infection may drive Th1-and Th17-biased immune responses against allergens during AAD.…”

Section: Discussionmentioning

confidence: 60%

Chlamydial Respiratory Infection during Allergen Sensitization Drives Neutrophilic Allergic Airways Disease

Horvat

Starkey

Kim

et al. 2010

The Journal of Immunology

108

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Section: Discussionmentioning

confidence: 60%

Chlamydial Respiratory Infection during Allergen Sensitization Drives Neutrophilic Allergic Airways Disease

Horvat

Starkey

Kim

et al. 2010

The Journal of Immunology

108

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“…Because different experimental models have implicated Th1 (25,26) and Th2 (27,28) factors as being important in the development of AHR, we also tested whether IFN-g KO mice (deficient in Th1 responses) and IL-4 receptor KO mice (deficient in Th2 responses) would develop AHR after Pneumocystis inoculation. In both mouse knockouts, however, AHR was only slightly, but not significantly, reduced from that seen in wildtype BALB/c mice.…”

Section: Investigation Of Essential Factors In the Early Inflammatorymentioning

confidence: 99%

Pneumocystis Elicits a STAT6-Dependent, Strain-Specific Innate Immune Response and Airway Hyperresponsiveness

Swain

Meissner²,

Siemsen³

et al. 2012

Am J Respir Cell Mol Biol

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It is widely held that exposure to pathogens such as fungi can be an agent of comorbidity, such as exacerbation of asthma or chronic obstructive pulmonary disease. Although many studies have examined allergic responses to fungi and their effects on pulmonary function, the possible pathologic implications of the early innate responses to fungal pathogens have not been explored. We examined early responses to the atypical fungus Pneumocystis in two common strains of mice in terms of overall immunological response and related pathology, such as cell damage and airway hyperresponsiveness (AHR). We found a strong strain-specific response in BALB/c mice that included recruitment of neutrophils, NK, NKT, and CD4 T cells. This response was accompanied by elevated indicators of lung damage (bronchoalveolar lavage fluid albumin and LDH) and profound AHR. This early response was absent in C57BL/6 mice, although both strains exhibited a later response associated with the clearance of Pneumocystis. We found that this AHR could not be attributed exclusively to the presence of recruited neutrophils, NKT, NK, or CD4 cells or to the actions of IFN-g or IL-4. However, in the absence of STAT6 signaling, AHR and inflammatory cell recruitment were virtually absent. Gene expression analysis indicated that this early response included activation of several transcription factors that could be involved in pulmonary remodeling. These results show that exposure to a fungus such as Pneumocystis can elicit pulmonary responses that may contribute to morbidity, even without prior sensitization, in the context of certain genetic backgrounds.Keywords: STAT6; airway hyperresponsiveness; Pneumocystis; pulmonary inflammation; strain-specificThe immunological response to respiratory pathogens is normally calibrated to eliminate an infection without causing overt collateral damage to the respiratory tissue. In spite of this, an overexuberant or misdirected immune response can have pathological outcomes. This can range from phenomena that are transient and typically moderate, such as elevated airway hyperresponsiveness (AHR), to those that are permanent and progressive, such as pulmonary fibrosis. The health effects of these immunological responses depend on the context of the infection; those that are comorbid with other acute or chronic pulmonary conditions may incite serious respiratory distress in that context when otherwise they might have little noticeable effect.One area in which the effects of comorbid respiratory illnesses are especially relevant is that of exacerbation of preexisting asthma or chronic obstructive pulmonary disease (COPD). Many potential pathogens have been implicated as causing exacerbation; the most well known are various viruses, including rhinovirus, metapneumovirus, and respiratory syncytial virus (1). Several respiratory bacteria, most notably the atypical bacteria Mycoplasma pneumoniae and Chlamydia pneumoniae, have also been implicated in the exacerbation of asthma symptoms (2). Common fungi have also been widely imp...

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“…Studies using mouse models have provided conflicting results about the potential role of Th1 cells and IFNc in airway inflammation and AHR. In some studies, Th1 cells and IFN-c were found to dampen allergic airway inflammation [56], whereas Th1 cells and IFN-c were found to have proinflammatory effects in other studies [57][58][59]. In a mouse model of virally induced AHR and airway remodelling, there was no attenuation of these parameters in IFN-c-deficient mice [60].…”

Section: Th2 Cells Asthma and Atopymentioning

confidence: 99%

T-helper cell type-2 regulation in allergic disease

Georas

Guo

Fanis

et al. 2005

European Respiratory Journal

151

101

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Substantial experimental evidence now supports the notion that allergic diseases are characterised by a skewing of the immune system towards a T-helper cell type-2 (Th2) phenotype.Studies using both human and mouse model systems have provided key evidence for the role that Th2 cytokines play in driving many of the hallmarks of allergic inflammation. Furthermore, the signalling pathways by which Th2 cytokines exert their effects on airway target cells are rapidly being elucidated, and antagonists of the Th2 pathway are under active development.In this review, the current knowledge of the role of T-helper cell type-2 cells in asthma is summarised, focusing on how and where T-helper cell type-2 cells differentiate from naïve precursors. The signalling molecules and transcription factors involved in T-helper cell type-2 differentiation will be reviewed in detail, in an attempt to translate studies using genetically modified mice into meaningful insights about asthma and other allergic diseases.

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TH1-mediated airway hyperresponsiveness independent of neutrophilic inflammation

Cited by 67 publications

References 30 publications

Chlamydial Respiratory Infection during Allergen Sensitization Drives Neutrophilic Allergic Airways Disease

Chlamydial Respiratory Infection during Allergen Sensitization Drives Neutrophilic Allergic Airways Disease

Pneumocystis Elicits a STAT6-Dependent, Strain-Specific Innate Immune Response and Airway Hyperresponsiveness

T-helper cell type-2 regulation in allergic disease

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