Airway macrophages as the guardians of tissue repair in the lung

Abstract

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.

Combined Collagen-Induced Arthritis and Organic Dust-Induced Airway Inflammation to Model Inflammatory Lung Disease in Rheumatoid Arthritis

“…Amphiregulin remained elevated with coexposure in the lung tissues, which is interpreted to be supportive of evidence towards interstitial disease. Macrophages have also been implicated in promoting lung fibrosis . Moreover, others have shown that the elimination of CD11b hi macrophages protects mice from bleomycin‐induced fibrosis .…”

“…Macrophages have also been implicated in promoting lung fibrosis. (42) Moreover, others have shown that the elimination of CD11b hi macrophages protects mice from bleomycin-induced fibrosis. (43) Interestingly, there was evidence that arthritis induction alone impacted the lung environment as CIA increased activated lung CD11c + CD11b hi macrophages that could work to modulate lung inflammation.…”

COVID‐19: searching for clues among other respiratory viruses

“…Lung‐resident macrophages play an integral role in maintaining homeostasis in the lungs and responding to viral pathogens, as outlined in a review by Puttur et al (③ in Figure 1). 4 Upon challenge, lung‐resident macrophages are highly phagocytic and are primary inductors of innate immune defenses through proinflammatory cytokine signaling and stimulation of protective antibody responses.…”

Neutrophil–macrophage cooperation and its impact on tissue repair

“…Inadequate repair mechanisms (such as those that occur during chronic inflammation or as a result of inappropriate macrophage function) can lead to nonresolving injury or fibrosis. Fibrotic tissues lose their flexibility because of excess deposition of ECM components including collagen, in a process that is known to be transforming growth factor beta dependent, 9 and more recently has been described to involve IL-17 10,11 (please see the review by Puttur et al on fibrosis in this issue for more details 66 ).…”