CD11b immunophenotyping identifies inflammatory profiles in the mouse and human lungs

• Published in: Mucosal immunology Vol. 9; no. 2; pp. 550 - 563
• Main Authors: Duan, M, Steinfort, D P, Smallwood, D, Hew, M, Chen, W, Ernst, M, Irving, L B, Anderson, G P, Hibbs, M L
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2016; Elsevier Limited
• Subjects: 631/1647/1407/1492; 631/250/2504/342/1927; 631/250/256; 692/699/1785; Allergology; Animals; Antibodies; Antibodies, Neutralizing - pharmacology; Asthma - diagnosis; Asthma - immunology; Asthma - pathology; Biomarkers - metabolism; Biomedical and Life Sciences; Biomedicine; CD11b Antigen - genetics; CD11b Antigen - immunology; Disease Models, Animal; Flow Cytometry; Gastroenterology; Gene Expression; Humans; Immunity, Innate; Immunology; Immunophenotyping; Lung - immunology; Lung - pathology; Macrophage Activation - drug effects; Macrophages, Alveolar - immunology; Macrophages, Alveolar - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Orthomyxoviridae - immunology; Orthomyxoviridae Infections - diagnosis; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - pathology; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases - deficiency; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases - genetics; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases - immunology; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - immunology; Pulmonary Disease, Chronic Obstructive - pathology; Pulmonary Eosinophilia - diagnosis; Pulmonary Eosinophilia - immunology; Pulmonary Eosinophilia - pathology
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2015.84

The development of easily accessible tools for human immunophenotyping to classify patients into discrete disease endotypes is advancing personalized therapy. However, no systematic approach has been developed for the study of inflammatory lung diseases with often complex and highly heterogeneous disease etiologies. We have devised an internally standardized flow cytometry approach that can identify parallel inflammatory alveolar macrophage phenotypes in both the mouse and human lungs. In mice, lung innate immune cell alterations during endotoxin challenge, influenza virus infection, and in two genetic models of chronic obstructive lung disease could be segregated based on the presence or absence of CD11b alveolar macrophage upregulation and lung eosinophilia. Additionally, heightened alveolar macrophage CD11b expression was a novel feature of acute lung exacerbations in the SHIP-1 −/− model of chronic obstructive lung disease, and anti-CD11b antibody administration selectively blocked inflammatory CD11b pos but not homeostatic CD11b neg alveolar macrophages in vivo . The identification of analogous profiles in respiratory disease patients highlights this approach as a translational avenue for lung disease endotyping and suggests that heterogeneous innate immune cell phenotypes are an underappreciated component of the human lung disease microenvironment.