Immune and microbial signatures in immunocompetent and immunocompromised patients with pneumonia

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Abstract

Background Pneumonia is a common acute respiratory infection that contributes to significant mortality and morbidity worldwide. The disruption of the airway microbiome in respiratory infection has been extensively reported. However, whether the changes in respiratory tract microbial communities during pneumonia were related to disease severity remains elusive. Herein, we aimed to investigate the correlation between the changes in airway microbiome and immune response in pneumonia patients. Methods We performed metagenomic and metatranscriptomic sequencing on immunocompetent (ICO) and immunocompromised host (ICH) with pneumonia using bronchoalveolar lavage fluid (BALF), blood, sputum, and swab samples. Results Compared to ICO patients with pneumonia, ICH patients had higher Pneumonia Severity Index (PSI) score. BALF metagenomic and metatranscriptomic sequencing showed higher microbial diversity in ICH patients, while ICH patients exhibited lower microbial diversity in sputum samples. Additionally, pneumonia patients with different PSI scores exhibited different microbial communities. Relative abundance of Human Gammaherpesvirus 4 (EBV) was positively correlated with PSI score. For ICH patients, BALF metatranscriptomic sequencing found 183 up-regulated genes and 85 down-regulated genes in EBV-detected group compared with EBV not-detected group, while there was no significant difference in ICO patients, indicating that EBV might be reactivated in ICH patients, while EBV might be latent in ICO patients. In ICH patients, we observed significant down-regulation of immune related genes and interferon stimulated genes in EBV-detected group compared to the not-detected group, including CSF1R , CXCR6 , IL10 , IL16 , and TNFRSF25 . Co-occurrence network analysis found positive correlations between EBV and Citrobacter freundii or Campylobacter concisus , indicating that synergistic effects on exacerbating the severity of pneumonia might exist between EBV and these two microbes. Conclusion EBV might be considered as a microbial signature for disease severity, which could regulate immune-related signaling pathways. Notably, we unravel that EBV presence might inhibit the immune response of hosts, reduce anti-inflammatory responses, and increase the possibilities of infections caused by other pathogens, exacerbating the pneumonia severity.

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