Understanding the function and behaviour of alveolar macrophages
Date
2021-04-28
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Abstract
Humans breathe in more than 10,000 liters of non-sterile air daily. This necessitates a constant interface of the lungs with the outside environment. Importantly, this process can allow pathogens, allergens, or other immunogenic moieties access into the lungs which can lead to injury or inflammation. Interestingly, despite this imminent threat, the lungs in most healthy individuals are kept free of pathogens and inflammation. The mechanisms by which such a feat is accomplished are still being uncovered. One important player in this regard is the resident phagocyte of the alveoli- the alveolar macrophages (AMs). These phagocytic cells have been identified as being crucial in maintaining the alveolar homeostasis. Interestingly, the alveoli have been proposed to outnumber AMs, leading to many alveoli that are devoid of AMs at any given point in time. Importantly, the current literature suggests that AMs, like most tissue resident macrophages, are sessile. If so, the numerical disadvantage could be exploited by pathogens that are breathed in, unless immune cells from the blood stream intervened. However, this would translate to omnipresent and persistent inflammation. Using in vivo real-time intravital imaging of the alveoli, we observed AMs crawling in and between the alveoli using the Pores of Kohn. Importantly, these AMs sensed, chemotaxed (via C5a and FPR1 dependent mechanism) and phagocytosed inhaled bacterial pathogens such as P. aeruginosa and S. aureus, cloaking the bacteria from neutrophils. Impairing AM chemotaxis towards bacteria, induced superfluous neutrophil recruitment leading to inappropriate inflammation and injury of the lungs. Additionally, in disease contexts such as viral infection or LPS mediated inflammation, AM behaviour was markedly altered which led to decreased bacterial capture and increased secondary co-infections. Collectively, the observations made in this thesis elucidate a crucial mechanism by which AMs keep the alveoli free of pathogens and inflammation leading to a significant advancement in the understanding of alveolar macrophage behaviour and function.
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Keywords
Immunology, alveolar macrophage, intravital microscopy
Citation
Neupane, A. S. (2021). Understanding the function and behaviour of alveolar macrophages (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.