A gammaherpesvirus provides protection against allergic asthma by inducing the replacement of resident alveolar macrophages with regulatory monocytes

• Published in: Nature immunology Vol. 18; no. 12; pp. 1310 - 1320
• Main Authors: Machiels, Bénédicte, Dourcy, Mickael, Xiao, Xue, Javaux, Justine, Mesnil, Claire, Sabatel, Catherine, Desmecht, Daniel, Lallemand, François, Martinive, Philippe, Hammad, Hamida, Guilliams, Martin, Dewals, Benjamin, Vanderplasschen, Alain, Lambrecht, Bart N, Bureau, Fabrice, Gillet, Laurent
• Format: Journal Article Web Resource
• Language: English
• Published: New York Nature Publishing Group US 01.12.2017; Nature Publishing Group
• Subjects: 13/1; 13/106; 13/21; 13/31; 14/1; 49/31; 49/91; 631/250/2504/342/1927; 631/250/255/2514; 631/326/596; 64/60; 692/699/249/2510/31; Adoptive Transfer; Allergic diseases; Alveoli; Animals; Asthma; Asthma - immunology; Asthma - therapy; Biomedicine; Care and treatment; Cell Line; Children; Complications and side effects; Cricetinae; Dendritic cells; Dendritic Cells - immunology; Development and progression; Embryos; Female; Hay fever; Helper cells; Herpesviridae Infections - immunology; Herpesviridae Infections - virology; Herpesvirus infections; House dust; Hygiene; Immunology; Infections; Infectious Diseases; Life sciences; Lungs; Lymphocytes; Lymphocytes T; Macrophages; Macrophages, Alveolar - cytology; Macrophages, Alveolar - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Microbiologie; Microbiology; Monocytes; Monocytes - immunology; Pyroglyphidae - immunology; Rhadinovirus - immunology; Sciences du vivant; Th2 Cells - immunology; Th2 Cells - transplantation
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/ni.3857

Gillet and colleagues find that infection with a gammaherpesvirus confers strong and lasting protection against airway allergy through the replacement of lung-resident alveolar macrophages with recruited regulatory monocytes of bone marrow origin. The hygiene hypothesis postulates that the recent increase in allergic diseases such as asthma and hay fever observed in Western countries is linked to reduced exposure to childhood infections. Here we investigated how infection with a gammaherpesvirus affected the subsequent development of allergic asthma. We found that murid herpesvirus 4 (MuHV-4) inhibited the development of house dust mite (HDM)-induced experimental asthma by modulating lung innate immune cells. Specifically, infection with MuHV-4 caused the replacement of resident alveolar macrophages (AMs) by monocytes with regulatory functions. Monocyte-derived AMs blocked the ability of dendritic cells to trigger a HDM-specific response by the T H 2 subset of helper T cells. Our results indicate that replacement of embryonic AMs by regulatory monocytes is a major mechanism underlying the long-term training of lung immunity after infection.