Sjoerd T. T. Schetters
Floris Dammeijer
Christophe J. Desmet- 1Center for Inflammation Research, Flanders Institute for Biotechnology, Ghent, Belgium
- 2Department of Internal Medicine and Pediatrics, Ghent University, Belgium, Ghent, Belgium
- 3Department of Pulmonary Medicine, Erasmus Medical Center, Rotterdam, Netherlands
- 4Laboratory of Tumor Immunology, Department of Medical Oncology, Cancer Institute, Erasmus Medical Center, Rotterdam, Netherlands
- 5Laboratory of Cellular and Molecular Immunology, GIGA Inflammation, Infection and Immunity, GIGA Institute, University of Liège, Liège, Belgium
- 6Laboratory of Pneumology, GIGA Inflammation, Infection and Immunity, GIGA Institute, University of Liège, Liège, Belgium
Editorial on the Research Topic
The development and plasticity of myeloid immunity in the lung
The immune system of the respiratory tract comprises a wide variety of myeloid cells, including macrophages, monocytes, mast cells, basophils, neutrophils and eosinophils. Far from their historic view as invariant terminal effector cells, myeloid cells can respond to different types of environmental insults through plastic adaptation of their development and function. In the respiratory tract, no other cell better illustrates this plasticity than the lung macrophages (1). For example, alveolar macrophages (AMs) are long-lived motile cells in the alveolar space, functioning as sentinels that scavenge innocuous airborne antigens or potentially harmful pathogens in the steady-state. In doing so, AMs are critical in maintaining homeostasis and preventing unnecessary inflammation in the delicate airways.
In this Research Topic, Sabatel and Bureau argue that this maintenance is an active and tightly controlled regulatory mechanism that counteracts immunostimulatory processes. AMs and lung-resident interstitial macrophages have been shown to differentially mediate immune tolerance to harmless antigens, while also being able to launch full-blown inflammation when the homeostatic threshold has been exceeded. Respiratory viral infections and allergic inflammation are characterized by recruitment of inflammatory granulocytes like eosinophils and neutrophils, and may even result in complete loss of AMs. Indeed, Feo-Lucas et al. elegantly show that allergic inflammation induced by exposure to respiratory house dust mite (HDM) leads to loss of tissue-resident AMs and the consecutive replacement of long-lived monocyte-derived AMs. This was accompanied by extensive alveolar damage, resulting in reduced gas exchange and surfactant dysfunction. In a similar effort, Draijer et al. investigate the temporal changes in AMs and IMs upon HDM exposure. AMs seemed to proliferate and polarize to a type 2 phenotype upon HDM re-challenge, expressing YM-1.
The inflammatory insults induced by viral infections or allergic inflammation are not without their long-term consequences, as is extensively summarized by (Rodriguez-Rodriguez et al.). They illustrate how the function of long-lived macrophages, including AMs, is dictated by origin, location and previous immunological experience. Future research will need to take these factors into account, since the exact differential role of infiltrating monocytes and tissue-resident macrophages remains an intense matter of debate (2–4). Especially with research aiming to reprogram resident macrophages or infiltrating monocytes as a therapeutic option, it is critical to understand their origin and spatio-temporal control (5–7).
The capacity of AMs to scavenge pathogens or dead cells has been suggested to be their main function in homeostasis and a failure to do so may result in pathology. In this regard, Slimmen et al. provide an interesting description of AMs derived from fresh alveolar lavages from a cohort of pediatric cystic fibrosis patients. They show that AMs from CF patients express lower levels of phagocytic receptors, possibly leading to inefficient clearance of debris or dead neutrophils in CF pathology. Indeed, the ability of AMs to cloak the alveolar space from pathogenic signals prevents neutrophilia (8).
Finally, in this Research Topic, Wang et al. review the current literature on neutrophil (dys)function during acute respiratory distress syndrome (ARDS), a pathological state of respiratory failure associated with severe COVID infection and bacterial sepsis. It is worth noting that although neutrophils are considered short-lived inflammatory cells, in chronic pathological conditions (like asthma, COVID-19 or brain tumors) neutrophils can survive in tissues for extended periods of time and assume a variety of persistent phenotypes (9).
The spatio-temporal control of the myeloid innate immune system remains a prolific topic of investigation in airway diseases. Future research aimed at understanding its development from (early-life) progenitors in interaction with the local niche will undoubtedly further our understanding and provide new avenues for therapeutic interventions.
Author contributions
SS: Writing – original draft, Writing – review & editing. FD: Writing – review & editing. CD: Writing – original draft, Writing – review & editing.
Funding
The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
Conflict of interest
CD reports salary from Le Fonds de la Recherche Scientifique – FNRS Belgium, consulting fees in Advisory Board on eosinophil research from AstraZeneca and lecture fees from GSK for presentation at several scientific symposia.
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
1. Aegerter H, Lambrecht BN, Jakubzick CV. Biology of lung macrophages in health and disease. Immunity (2022) 55:1564–80. doi: 10.1016/j.immuni.2022.08.010
2. Wang T, Zhang J, Wang L, Wang Y, Li Y, Yao Y. Reply to: The role of recruitment versus training in influenza-induced lasting changes to alveolar macrophage function. Nat Immunol (2023) 24:1642–4. doi: 10.1038/s41590-023-01603-0
3. Wang T, Zhang J, Wang Y, Li Y, Wang L, Yu Y, Yao Y. Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs. Nat Immunol (2023) 24:423–38. doi: 10.1038/s41590-023-01428-x
4. Iliakis CS, Kulikauskaite J, Aegerter H, Li F, Piattini F, Jakubzick CV, et al. The role of recruitment versus training in influenza-induced lasting changes to alveolar macrophage function. Nat Immunol (2023) 24:1639–41. doi: 10.1038/s41590-023-01602-1
5. Cheong J-G, Ravishankar A, Sharma S, Parkhurst CN, Grassmann SA, Wingert CK, et al. Epigenetic memory of coronavirus infection in innate immune cells and their progenitors. Cell (2023) 186:3882–3902.e24. doi: 10.1016/j.cell.2023.07.019
6. Ding C, Shrestha R, Zhu X, Geller AE, Wu S, Woeste MR, et al. Inducing trained immunity in pro-metastatic macrophages to control tumor metastasis. Nat Immunol (2023) 24:239–54. doi: 10.1038/s41590-022-01388-8
7. Zhang X, Li S, Malik I, Do MH, Ji L, Chou C, et al. Reprogramming tumour-associated macrophages to outcompete cancer cells. Nature (2023) 619:616–23. doi: 10.1038/s41586-023-06256-5
8. Neupane AS, Willson M, Chojnacki AK, Silva Castanheira FVE, Morehouse C, Carestia A, et al. Patrolling alveolar macrophages conceal bacteria from the immune system to maintain homeostasis. Cell (2020) 183:110–125.e11. doi: 10.1016/j.cell.2020.08.020
Keywords: alveolar macrophage, innate immunity, lung immune cells, myeloid plasticity, asthma, ARDS (acute respiratory disease syndrome), respiratory viral and bacterial infections
Citation: Schetters STT, Dammeijer F and Desmet CJ (2023) Editorial: The development and plasticity of myeloid immunity in the lung. Front. Immunol. 14:1332852. doi: 10.3389/fimmu.2023.1332852
Received: 03 November 2023; Accepted: 09 November 2023;
Published: 16 November 2023.
Edited and Reviewed by:
Hani S. Mousa, University of Cambridge, United KingdomCopyright © 2023 Schetters, Dammeijer and Desmet. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Sjoerd T. T. Schetters, c2pvZXJkc0BpcmMudmliLXVnZW50LmJl