Our immune system, consisting of proteins, microbes, and specialized immune cells known as white blood cell cells, is crucial for survival. Macrophages are a white blood cell engulfing and destroying any foreign invader, such as viruses or bacteria, it finds in the host in a process known as phagocytosis. Alveolar macrophages (AMs), found primarily in the respiratory tract, are the guards of the airways performing phagocytosis and releasing inflammatory proteins known as cytokines, to recruit other immune cells. However, this response can go awry due to an infection, genetics or autoimmune disorders causing a ‘cytokine storm’, an over-production of cytokines leading to a hyperactive immune system that starts to attack healthy tissue, as seen in COVID-19 patients. It is unclear how this cytokine storm is avoided, and even more importantly why some patients are predisposed to it occurring. Now, a study from researchers led by Columbia University identifies a previously unknown subset of AMs, dubbed nerve and airway associated macrophages or NAMs, specialized to the airways of the lungs to provide pulmonary immunoregulation of an overactive AM-induced inflammatory response. The team states the newly discovered NAMs regulate the cytokine-based inflammation produced by AMs during a lung infection and could provide new information on cytokine storms linked to lung damage and death in influenza or coronavirus patients. The study is published in the journal Science Immunology.
Previous studies show AMs clear the respiratory system of infectious, toxic, or allergic particles through the secretion of various proteins and the use of phagocytosis to eliminate small invasions. When faced with larger numbers of infectious particles or a harsher strain of microbe AMs secrete cytokines to recruit the rest of the immune system. Cytokines are small proteins produced by the immune system to coordinate immunity and trigger inflammation. However, this inflammatory response can become overactive, for example when COVID-19 enters the pulmonary system, causing a cytokine storm. This is where excessive or uncontrolled levels of cytokines are released into the bloodstream, activating more immune cells, resulting in hyper inflammation, seriously harming or even killing the patient. The current study identifies a previously unknown group of pulmonary macrophages dubbed NAMs implicated in the moderation of hyper inflammation in the lungs caused by the immune response to pathogens.
The current study uses live-cell imaging in live mice to identify and analyze NAMs primarily grouped around the sympathetic pulmonary nerves and airways. A complete set of RNA transcripts produced by the genome of grouped and single NAMs was sequenced using high-throughput methods helped to establish that NAMs are distinct from other macrophage species unique to the lungs. Results show NAMs are embryonically derived, self-renewing, and are constantly expressing genes responsible for regulating the immune system whether they’re in equilibrium or an inflammatory state.
When mice were given the flu to examine the role of NAMs during infection the lab observed that NAMs increased rapidly in number following infection in normal mice. Results show in mice unable to produce NAMs, infection triggered an overwrought immune response producing an excess of inflammatory cytokines and tissue-infiltrating immune cells. The group concludes AMs help clear the influenza infection, with NAMs working alongside them to help regulate and suppress inflammatory responses.
The team surmises they have identified previously unrecorded macrophages exclusive to the lungs responsible for maintaining immune and tissue homeostasis under inflammation. The researchers state further investigation is needed to harness the immunoregulatory power of these macrophages against infectious pathogens causing cytokine storms such as COVID-19.
Source: Technology Networks
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