Alveolar macrophages are sentinels of murine pulmonary homeostasis following inhaled antigen challenge

Mathie, Sara A.; Dixon, Kate L.; Walker, Simone A.; Tyrrell, Victoria J.; Mondhe, Madhav; O'Donnell, Valerie Bridget; Gregory, Lisa G.; Lloyd, Clare M.

doi:10.1111/all.12536

Cited by 73 publications

(66 citation statements)

References 31 publications

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“…In the allergic models, MF depletion attenuated, rather than enhanced, goblet cell metaplasia and other Th2 inflammatory responses in the absence of bacterial pneumonia (25,39,40).…”

Section: Discussionmentioning

confidence: 96%

Neonatal Pulmonary Macrophage Depletion Coupled to Defective Mucus Clearance Increases Susceptibility to Pneumonia and Alters Pulmonary Immune Responses

Saini

Wilkinson²,

Terrell³

et al. 2016

Am J Respir Cell Mol Biol

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Resident immune cells (e.g., macrophages [MFs]) and airway mucus clearance both contribute to a healthy lung environment. To investigate interactions between pulmonary MF function and defective mucus clearance, a genetic model of lysozyme M (LysM) promoter-mediated MF depletion was generated, characterized, and crossed with the sodium channel b subunit transgenic (Scnn1b-Tg) mouse model of defective mucus clearance. Diphtheria toxin A-mediated depletion of LysM 1 pulmonary MFs in wild-type mice with normal mucus clearance resulted in lethal pneumonia in 24% of neonates. The pneumonias were dominated by Pasteurella pneumotropica and accompanied by emaciation, neutrophilic inflammation, and elevated Th1 cytokines. The incidence of emaciation and pneumonia reached 51% when LysM 1 MF depletion was superimposed on the airway mucus clearance defect of Scnn1b-Tg mice. In LysM 1 MF-depleted Scnn1b-Tg mice, pneumonias were associated with a broader spectrum of bacterial species and a significant reduction in airway mucus plugging. Bacterial burden (CFUs) was comparable between Scnn1b-Tg and nonpneumonic LysM 1 MF-depleted Scnn1b-Tg mice. However, the nonpneumonic LysM 1 MF-depleted Scnn1b-Tg mice exhibited increased airway inflammation, the presence of neutrophilic infiltration, and increased levels of inflammatory cytokines in bronchoalveolar lavage fluid compared with Scnn1b-Tg mice. Collectively, these data identify key MF-mucus clearance interactions with respect to both infectious and inflammatory components of muco-obstructive lung disease.

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“…In the allergic models, MF depletion attenuated, rather than enhanced, goblet cell metaplasia and other Th2 inflammatory responses in the absence of bacterial pneumonia (25,39,40).…”

Section: Discussionmentioning

confidence: 96%

Neonatal Pulmonary Macrophage Depletion Coupled to Defective Mucus Clearance Increases Susceptibility to Pneumonia and Alters Pulmonary Immune Responses

Saini

Wilkinson²,

Terrell³

et al. 2016

Am J Respir Cell Mol Biol

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“…The removal of AMs in mice worsens lung function and Th2 inflammation; furthermore, transfer of healthy AMs protected against asthma-like symptoms 60. Depletion of AMs during allergic disease delayed inflammatory resolution and there was a decrease in the production of the immune regulatory cytokine IL-27 61. These data suggest that macrophages are capable of dictating the pulmonary immune response to inhaled allergen and furthermore, that allergen exposure may impair the ability of macrophages to maintain lung immune homoeostasis 62.…”

Section: Asthma and Allergic Airways Diseasementioning

confidence: 99%

Pulmonary macrophages: key players in the innate defence of the airways

Byrne

Mathie

Gregory

et al. 2015

Thorax

403

313

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Macrophages are the most numerous immune-cells present in the lung environment under homoeostatic conditions and are ideally positioned to dictate the innate defence of the airways. Pulmonary macrophage populations are heterogeneous and demonstrate remarkable plasticity, owing to variations in origin, tissue residency and environmental influences. Lung macrophage diversity facilitates considerable specialisation, aids efficient responses to environmental signals and allows rapid alterations in phenotype and physiology in response to a plethora of cytokines and microbial signals. This review describes pulmonary macrophage origins, phenotypes, roles in diseases of the airways and implications for the treatment of respiratory disease.

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“…In fact, in murine models alveolar macrophage (AM) depletion leads to a high degree of inflammation and an increased production of IgE [17], suggesting an association of AMs with progression of the asthmatic status. They act as a sentinel for cellular defence against respiratory pathogens.…”

Section: Immune Response During Allergic Asthmamentioning

confidence: 99%

Allergic asthma: an overview of metabolomic strategies leading to the identification of biomarkers in the field

Villaseñor

Rosace

Obeso

et al. 2017

Clin Experimental Allergy

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Allergic asthma is a prominent disease especially during childhood. Indoor allergens, in general, and particularly house dust mites (HDM) are the most prevalent sensitizers associated with allergic asthma. Available data show that 65-130 million people are mite-sensitized world-wide and as many as 50% of these are asthmatic. In fact, sensitization to HDM in the first years of life can produce devastating effects on pulmonary function leading to asthmatic syndromes that can be fatal. To date, there has been considerable research into the pathological pathways and structural changes associated with allergic asthma. However, limitations related to the disease heterogeneity and a lack of knowledge into its pathophysiology have impeded the generation of valuable data needed to appropriately phenotype patients and, subsequently, treat this disease. Here, we report a systematic and integral analysis of the disease, from airway remodelling to the immune response taking place throughout the disease stages. We present an overview of metabolomics, the management of complex multifactorial diseases through the analysis of all possible metabolites in a biological sample, obtaining a global interpretation of biological systems. Special interest is placed on the challenges to obtain biological samples and the methodological aspects to acquire relevant information, focusing on the identification of novel biomarkers associated with specific phenotypes of allergic asthma. We also present an overview of the metabolites cited in the literature, which have been related to inflammation and immune response in asthma and other allergy-related diseases.

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Alveolar macrophages are sentinels of murine pulmonary homeostasis following inhaled antigen challenge

Cited by 73 publications

References 31 publications

Neonatal Pulmonary Macrophage Depletion Coupled to Defective Mucus Clearance Increases Susceptibility to Pneumonia and Alters Pulmonary Immune Responses

Neonatal Pulmonary Macrophage Depletion Coupled to Defective Mucus Clearance Increases Susceptibility to Pneumonia and Alters Pulmonary Immune Responses

Pulmonary macrophages: key players in the innate defence of the airways

Allergic asthma: an overview of metabolomic strategies leading to the identification of biomarkers in the field

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