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Myeloid Cells in Asthma

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  • Authors: Bart N. Lambrecht1,2, Emma K. Persson3, Hamida Hammad4,5
  • Editor: Siamon Gordon6
    Affiliations: 1: VIB Center for Inflammation Research, Ghent University, 9000 Gent, Belgium; 2: Department of Pulmonary Medicine, Ghent University Hospital, 9000 Gent, Belgium; 3: VIB Center for Inflammation Research, Ghent University, 9000 Gent, Belgium; 4: VIB Center for Inflammation Research, Ghent University, 9000 Gent, Belgium; 5: Department of Pulmonary Medicine, Ghent University Hospital, 9000 Gent, Belgium; 6: Oxford University, Oxford, United Kingdom
  • Source: microbiolspec January 2017 vol. 5 no. 1 doi:10.1128/microbiolspec.MCHD-0053-2016
  • Received 27 September 2016 Accepted 02 December 2016 Published 20 January 2017
  • Bart N. Lambrecht, [email protected]
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  • Abstract:

    Asthma is a heterogeneous chronic inflammatory disorder of the airways, and not surprisingly, many myeloid cells play a crucial role in pathogenesis. Antigen-presenting dendritic cells are the first to recognize the allergens, pollutants, and viruses that are implicated in asthma pathogenesis, and subsequently initiate the adaptive immune response by migrating to lymph nodes. Eosinophils are the hallmark of type 2 inflammation, releasing toxic compounds in the airways and contributing to airway remodeling. Mast cells and basophils control both the early- and late-phase allergic response and contribute to alterations in smooth muscle reactivity. Finally, relatively little is known about neutrophils and macrophages in this disease. Although many of these myeloid cells respond well to treatment with inhaled steroids, there is now an increasing armamentarium of targeted biologicals that can specifically eliminate only one myeloid cell population, like eosinophils. It is only with those new tools that we will be able to fully understand the role of myeloid cells in chronic asthma in humans.

  • Citation: Lambrecht B, Persson E, Hammad H. 2017. Myeloid Cells in Asthma. Microbiol Spectrum 5(1):MCHD-0053-2016. doi:10.1128/microbiolspec.MCHD-0053-2016.


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Asthma is a heterogeneous chronic inflammatory disorder of the airways, and not surprisingly, many myeloid cells play a crucial role in pathogenesis. Antigen-presenting dendritic cells are the first to recognize the allergens, pollutants, and viruses that are implicated in asthma pathogenesis, and subsequently initiate the adaptive immune response by migrating to lymph nodes. Eosinophils are the hallmark of type 2 inflammation, releasing toxic compounds in the airways and contributing to airway remodeling. Mast cells and basophils control both the early- and late-phase allergic response and contribute to alterations in smooth muscle reactivity. Finally, relatively little is known about neutrophils and macrophages in this disease. Although many of these myeloid cells respond well to treatment with inhaled steroids, there is now an increasing armamentarium of targeted biologicals that can specifically eliminate only one myeloid cell population, like eosinophils. It is only with those new tools that we will be able to fully understand the role of myeloid cells in chronic asthma in humans.

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Image of FIGURE 1

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The early and late allergic response. This figure depicts the alterations in the airways, as well as the lung function alterations (measured as the amount of air being exhaled in 1 s in a forced expiratory maneuver, or FEV) in allergic patients before, during, and after an experimental allergen challenge. Before the challenge, the airways of asthmatics are hyperreactive (this does not always lead to reduced FEV). Minutes after allergen challenge, there is bronchoconstriction, and this is reflected by a drop in FEV that can sometimes be as much as 50% in very severe asthma attacks. This is called the early or immediate allergic response. After some 3 to 6 h, there is a second drop in FEV, this time accompanied by edema of the airway wall, cellular influx with inflammatory cells, and bronchoconstriction. This phase is called the late or delayed allergic response.

Source: microbiolspec January 2017 vol. 5 no. 1 doi:10.1128/microbiolspec.MCHD-0053-2016
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Image of FIGURE 2

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The cellular interplay of myeloid and lymphoid cells in allergic asthma. (Left) A first allergen exposure leads to activation of CD11b cDC2s. This activation is direct or indirect, because lung epithelial cells make cytokines like IL-1, IL-33, IL-25, TSLP, and GM-CSF that mature the DCs. The same cytokines also activate basophils and ILC2, which control immediate innate eosinophilia. After a few hours, DCs will also arrive in the draining mediastinal nodes, where they will polarize adaptive immune cells to become Th2, Th21, and Th17 cells. B cells will be induced to secrete IgE. (Right) A recall response to allergens, which occurs continuously in patients allergic to perennial allergens. Upon repeated encounter with allergens, tissue mast cells and basophils are armed with IgE and release immediate mediators into the lung tissue, causing bronchoconstriction and local edema. Monocyte-derived cells (DCs and activated macrophages) will also take up allergens via IgE and this time present these allergens locally to T effector cells and resident memory Th2 cells. These effector cells reach the lungs because of chemokine production by monocyte-derived cells. The effector lymphocytes will also produce loss of IL-5, which boosts the production of eosinophils. These eosinophils migrate into the lungs and cause damage to the lung epithelium. In some cases, particularly when there is a Th17 response, neutrophils also will accumulate in the lungs. PGD, prostaglandin D. Modified from reference 3 , with permission.

Source: microbiolspec January 2017 vol. 5 no. 1 doi:10.1128/microbiolspec.MCHD-0053-2016
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