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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. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling 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 colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype 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.

SUBMITTER: Mirchandani AS

PROVIDER: S-EPMC9174051 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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

Mirchandani Ananda S AS Jenkins Stephen J SJ Bain Calum C CC Sanchez-Garcia Manuel A MA Lawson Hannah H Coelho Patricia P Murphy Fiona F Griffith David M DM Zhang Ailiang A Morrison Tyler T Ly Tony T Arienti Simone S Sadiku Pranvera P Watts Emily R ER Dickinson Rebecca S RS Reyes Leila L Cooper George G Clark Sarah S Lewis David D Kelly Van V Spanos Christos C Musgrave Kathryn M KM Delaney Liam L Harper Isla I Scott Jonathan J Parkinson Nicholas J NJ Rostron Anthony J AJ Baillie J Kenneth JK Clohisey Sara S Pridans Clare C Campana Lara L Lewis Philip Starkey PS Simpson A John AJ Dockrell David H DH Schwarze Jürgen J Hirani Nikhil N Ratcliffe Peter J PJ Pugh Christopher W CW Kranc Kamil K Forbes Stuart J SJ Whyte Moira K B MKB Walmsley Sarah R SR

Nature immunology 20220527 6

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. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interfero ...[more]

PMID: 35624205

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Project description:BackgroundThe foodborne bacterium Listeria monocytogenes (Lm) causes a range of diseases, from mild gastroenteritis to invasive infections that have high fatality rate in vulnerable individuals. Understanding the population genomic structure of invasive Lm is critical to informing public health interventions and infection control policies that will be most effective especially in local and regional communities.MethodsWe sequenced the whole draft genomes of 936 Lm isolates from human clinical samples obtained in a two-decade active surveillance program across 58 counties in New York State, USA. Samples came mostly from blood and cerebrospinal fluid. We characterized the phylogenetic relationships, population structure, antimicrobial resistance genes, virulence genes, and mobile genetic elements.ResultsThe population is genetically heterogenous, consisting of lineages I-IV, 89 clonal complexes, 200 sequence types, and six known serogroups. In addition to intrinsic antimicrobial resistance genes (fosX, lin, norB, and sul), other resistance genes tetM, tetS, ermG, msrD, and mefA were sparsely distributed in the population. Within each lineage, we identified clusters of isolates with ≤ 20 single nucleotide polymorphisms in the core genome alignment. These clusters may represent isolates that share a most recent common ancestor, e.g., they are derived from the same contamination source or demonstrate evidence of transmission or outbreak. We identified 38 epidemiologically linked clusters of isolates, confirming eight previously reported disease outbreaks and the discovery of cryptic outbreaks and undetected chains of transmission, even in the rarely reported Lm lineage III (ST3171). The presence of animal-associated lineages III and IV may suggest a possible spillover of animal-restricted strains to humans. Many transmissible clones persisted over several years and traversed distant sites across the state.ConclusionsOur findings revealed the bacterial determinants of invasive listeriosis, driven mainly by the diversity of locally circulating lineages, intrinsic and mobile antimicrobial resistance and virulence genes, and persistence across geographical and temporal scales. Our findings will inform public health efforts to reduce the burden of invasive listeriosis, including the design of food safety measures, source traceback, and outbreak detection.

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

Publications

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

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