title: CD11b immunophenotyping identifies inflammatory profiles in the mouse and human lungs.
abstract: 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.
authors.affiliation: Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Australia.|Department of Surgery, University of Melbourne, Melbourne, Australia.|Ludwig Institute for Cancer Research, Melbourne, Australia.|Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Duan
authors.affiliation: Department of Respiratory Medicine, Royal Melbourne Hospital, Parkville, Australia.
authors.forename: D P
authors.initials: DP
authors.lastname: Steinfort
authors.affiliation: Department of Respiratory Medicine, Royal Melbourne Hospital, Parkville, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Smallwood
authors.affiliation: Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Parkville, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Hew
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Australia.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.affiliation: The Walter and Eliza Hall Institute for Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Ernst
authors.affiliation: Department of Respiratory Medicine, Royal Melbourne Hospital, Parkville, Australia.
authors.forename: L B
authors.initials: LB
authors.lastname: Irving
authors.affiliation: Department of Pharmacology, University of Melbourne, Melbourne, Australia.
authors.forename: G P
authors.initials: GP
authors.lastname: Anderson
authors.affiliation: Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Australia.
authors.forename: M L
authors.initials: ML
authors.lastname: Hibbs
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001249:Asthma / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate; D016130:Immunophenotyping; D008168:Lung / Q000276:immunology / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D011657:Pulmonary Eosinophilia / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology
chemical_list: D057134:Antibodies, Neutralizing; D015415:Biomarkers; D039481:CD11b Antigen; C000606433:Inpp5d protein, mouse; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases