Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation

ABSTRACT: Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. Here we showed that ARDS patients were hypoxaemic and monocytopenic within the first 48 hours of ventilation. Monocytopenia was also observed in mouse models of acute lung injury, in which tissue hypoxia drove the suppression of type I interferon signalling in the bone marrow. This impaired monopoiesis, resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of CSF1 in mice with hypoxic lung injury rescued the monocytopenia, altered the nature of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Monocyte, Blood

DISEASE(S): Adult Respiratory Distress Syndrome

SUBMITTER: Ananda Mirchandani  

LAB HEAD: Sarah Walmsley

PROVIDER: PXD033151 | Pride | 2022-08-12

REPOSITORIES: Pride