Congratulations to our Platform 1 Co-Lead Dr. Paul Kubes on this recent publication!
Using in vivo live imaging of infected lungs in animal models, Dr. Kubes‘ team and colleagues show that alveolar macrophages patrol the airways and capture inhaled bacteria, but their migration is impaired during viral infection. Their discoveries highlight the importance of finding out why this is happening with the hope to “develop targeted therapies to kickstart the macrophages into action again,” says Dr. Kubes.
Read more about Dr. Kubes’ insights, principal investigator of the study here and listen to Neupane Arpan, first author, explains their discovery.
Abstract
During respiration, humans breathe in more than 10,000 liters of non-sterile air daily, allowing some pathogens access to alveoli. Interestingly, alveoli outnumber alveolar macrophages (AMs), which favors alveoli devoid of AMs. If AMs, like most tissue macrophages, are sessile, then this numerical advantage would be exploited by pathogens unless neutrophils from the blood stream intervened. However, this would translate to omnipresent persistent inflammation. Developing in vivo real-time intravital imaging of alveoli revealed AMs crawling in and between alveoli using the pores of Kohn. Importantly, these macrophages sensed, chemotaxed, and, with high efficiency, phagocytosed inhaled bacterial pathogens such as P. aeruginosa and S. aureus, cloaking the bacteria from neutrophils. Impairing AM chemotaxis toward bacteria induced superfluous neutrophil recruitment, leading to inappropriate inflammation and injury. In a disease context, influenza A virus infection impaired AM crawling via the type II interferon signaling pathway, and this greatly increased secondary bacterial co-infection.
Publication: Patrolling Alveolar Macrophages Conceal Bacteria from the Immune System to Maintain Homeostasis. Neupane AS, Willson M, Chojnacki AK, Silva Castanheira FVE, Morehouse C, Carestia A, Keller AE, Peiseler M, DiGiandomenico A, Kelly MM, Amrein M, Jenne C, Thanabalasuriar A, Kubes P. Cell. 03 September 2020.
