Human asthma is characterized by more IRF5+ M1 and CD206+ M2 macrophages and less IL-10+ M2-like macrophages around airways compared with healthy airways

Draijer, Christina; Boorsma, Carian E.; Robbe, Patricia; Timens, Wim; Hylkema, Machteld N.; Hacken, Nick H. T. ten; Berge, Maarten van den; Postma, Dirkje S.; Melgert, Barbro N.

doi:10.1016/j.jaci.2016.11.020

Cited by 69 publications

(74 citation statements)

References 19 publications

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“…Adoptive transfer of IRF5‐deficient AM to wild‐type mice drives airway hyperreactivity at baseline and following antigen challenge . Patients with asthma have increased numbers of tissue IRF‐5‐positive macrophages compared to healthy controls and intriguingly asthmatic males have significantly more than females . Thus, allergen exposure may impair the immunoregulatory function of AM in allergic airways disease.…”

Section: Chronic Lung Diseasesmentioning

confidence: 99%

Airway macrophages as the guardians of tissue repair in the lung

2019

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The lungs present a challenging immunological dilemma for the host. Anatomically positioned at the environmental interface, they are constantly exposed to antigens, pollutants and microbes, while simultaneously facilitating vital gas exchange. Remarkably, the lungs maintain a functionally healthy state, ignoring harmless inhaled proteins, adapting to toxic environmental insults and limiting immune responses to allergens and pathogenic microbes. This functional strategy of environmental adaptation maintains immune defense, reduces tissue damage, and promotes and sustains lung immune tolerance. At steady state, airway macrophages produce low levels of cytokines, and suppress the induction of innate and adaptive immunity. These cells are primary initiators of lung innate immunity and possess high phagocytic activity to clear particulate antigens and apoptotic cell debris from the airways to regulate the response to infection and inflammation. In response to epithelial injury, resident and recruited macrophages drive tissue repair. In this review, we will focus on the functional importance of macrophages in tissue homeostasis and inflammation in the lung and highlight how environmental cues alter the plasticity and function of lung airway macrophages. We will also discuss mechanisms employed by pulmonary macrophages to promote resolution of tissue inflammation, and how and when this balance is perturbed, they contribute to pathological remodeling in acute and chronic infections and diseases such as asthma, idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.

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Section: Chronic Lung Diseasesmentioning

confidence: 99%

Airway macrophages as the guardians of tissue repair in the lung

2019

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“…Since AMs respond differently to these two groups of cytokines, it may be expected that different macrophage phenotypes could similarly coexist. Indeed, our recent investigation demonstrated the presence of a mix of macrophage phenotypes in both mouse models of allergic inflammation as well as in human asthmatics [48, 49•]. Such data have therefore motivated studies on the involvement of classically activated macrophages in asthma, with results suggesting diverse possible roles [50–52].…”

Section: “Unexpected” Macrophage Phenotype In Allergic Asthmamentioning

confidence: 99%

“…This would suggest that these macrophages might serve as a counter-regulatory mechanism to dampen inflammation. On the other hand, we observed by immunohistochemical analysis that the presence of higher numbers of macrophages expressing the IFNγ-activated transcription factor interferon regulatory factor 5 (IRF5) in bronchial biopsies of asthma patients was associated with more severe airflow obstruction (lower FEV 1 /FVC) [49•]. Thus, classical activation of macrophages may not only help prevent allergic sensitization, but may also promote the development of a more severe asthma phenotype in the context of established disease.…”

Section: “Unexpected” Macrophage Phenotype In Allergic Asthmamentioning

confidence: 99%

“…Examining the properties of normal AMs during health indeed revealed a predominantly anti-inflammatory phenotype. More IL-10+ macrophages were found in healthy mice and humans than in models of airway inflammation and in biopsies of asthmatics [48,49•,61]. The role of IL-10 in the immune system has been studied intensively, and this cytokine was found to be important in the resolution of airway inflammation [68, 69].…”

Section: Macrophage Phenotypes In Homeostasismentioning

confidence: 99%

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Alveolar Macrophages in Allergic Asthma: the Forgotten Cell Awakes

Draijer

Peters‐Golden

2017

Curr Allergy Asthma Rep

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Purpose of Review The role of alveolar macrophages in innate immune responses has long been appreciated. Here, we review recent studies evaluating the participation of these cells in allergic inflammation. Recent Findings Immediately after allergen exposure, monocytes are rapidly recruited from the bloodstream and serve to promote acute inflammation. By contrast, resident alveolar macrophages play a predominantly suppressive role in an effort to restore homeostasis. As inflammation becomes established after repeated exposures, alveolar macrophages can polarize across a continuum of activation phenotypes, losing their suppressive functions and gaining pathogenic functions. Summary Future research should focus on the diverse roles of monocytes/macrophages during various types and phases of allergic inflammation. These properties could lead us to new therapeutic opportunities.

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“…In allergic asthma, macrophages are considered to play a key role in inflammatory responses associated with lung injury, fibrosis and goblet cell hyperplasia and stimulating smooth muscle cell contraction and extracellular cell matrix degradation, contributing to airway remodelling. Increased numbers of mannose receptor (MR)+ macrophages (a surface marker for M2 macrophages) are found in the bronchial tissue of allergic asthmatic patients …”

Section: Helminths and Modulation Of Allergic Disease: The Role Of Immentioning

confidence: 99%

Worms: Pernicious parasites or allies against allergies?

McSorley

Chayé

Smits

2018

Parasite Immunology

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Type 2 immune responses are most commonly associated with allergy and helminth parasite infections. Since the discovery of Th1 and Th2 immune responses more than 30 years ago, models of both allergic disease and helminth infections have been useful in characterizing the development, effector mechanisms and pathological consequences of type 2 immune responses. The observation that some helminth infections negatively correlate with allergic and inflammatory disease led to a large field of research into parasite immunomodulation. However, it is worth noting that helminth parasites are not always benign infections, and that helminth immunomodulation can have stimulatory as well as suppressive effects on allergic responses. In this review, we will discuss how parasitic infections change host responses, the consequences for bystander immunity and how this interaction influences clinical symptoms of allergy.

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Human asthma is characterized by more IRF5+ M1 and CD206+ M2 macrophages and less IL-10+ M2-like macrophages around airways compared with healthy airways

Cited by 69 publications

References 19 publications

Airway macrophages as the guardians of tissue repair in the lung

Airway macrophages as the guardians of tissue repair in the lung

Alveolar Macrophages in Allergic Asthma: the Forgotten Cell Awakes

Worms: Pernicious parasites or allies against allergies?

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