Gammaherpesvirus Alters Alveolar Macrophages According to the Host Genetic Background and Promotes Beneficial Inflammatory Control over Pneumovirus Infection

• Published in: Viruses Vol. 14; no. 1; p. 98
• Main Authors: Gilliaux, Gautier, Desmecht, Daniel
• Format: Journal Article Web Resource
• Language: English
• Published: Switzerland MDPI AG 06-01-2022; Multidisciplinary Digital Publishing Institute (MDPI); MDPI
• Subjects: alveolar macrophages; Alveoli; animal models; Animals; Asthma; Bronchopneumonia; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Chemokines; Cytokines - metabolism; Early experience; Epstein-Barr virus; Female; gammaherpesvirus; Genetic Background; Genetic diversity; Herpesviridae Infections - genetics; Herpesviridae Infections - immunology; Herpesviridae Infections - pathology; Herpesviridae Infections - virology; Human health sciences; Immune response; Immune system; Immunity, Innate; Immunological memory; Immunologie & maladie infectieuse; Immunology & infectious disease; immunopathogenesis; Infections; Inflammation; Inflammation - immunology; innate and adaptive immunity; Innate immunity; Lethal dose; Leukocytes (neutrophilic); Lung - immunology; Lung - pathology; Lung - virology; Lungs; Macrophages; Macrophages, Alveolar - immunology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Monocytes - immunology; Pathogens; Phenotypes; Pneumococcal Infections - immunology; Pneumonia; pneumoviridae; Pneumovirus - immunology; Pneumovirus - physiology; Pneumovirus Infections - genetics; Pneumovirus Infections - immunology; Pneumovirus Infections - pathology; Pneumovirus Infections - virology; Respiratory syncytial virus; Rhadinovirus - immunology; Rhadinovirus - physiology; Sciences de la santé humaine; Sociodemographics; animal models; pneumoviridae; gammaherpesvirus; immunopathogenesis; inflammation; alveolar macrophages; innate and adaptive immunity
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v14010098

Human respiratory syncytial virus (hRSV) infection brings a wide spectrum of clinical outcomes, from a mild cold to severe bronchiolitis or even acute interstitial pneumonia. Among the known factors influencing this clinical diversity, genetic background has often been mentioned. In parallel, recent evidence has also pointed out that an early infectious experience affects heterologous infections severity. Here, we analyzed the importance of these two host-related factors in shaping the immune response in pneumoviral disease. We show that a prior gammaherpesvirus infection improves, in a genetic background-dependent manner, the immune system response against a subsequent lethal dose of pneumovirus primary infection notably by inducing a systematic expansion of the CD8
bystander cell pool and by modifying the resident alveolar macrophages (AMs) phenotype to induce immediate cyto/chemokinic responses upon pneumovirus exposure, thereby drastically attenuating the host inflammatory response without affecting viral replication. Moreover, we show that these AMs present similar rapid and increased production of neutrophil chemokines both in front of pneumoviral or bacterial challenge, confirming recent studies attributing a critical antibacterial role of primed AMs. These results corroborate other recent studies suggesting that the innate immunity cells are themselves capable of memory, a capacity hitherto reserved for acquired immunity.