title: Alveolar macrophages are a major determinant of early responses to viral lung infection but do not influence subsequent disease development.
abstract: Macrophages are abundant in the lower respiratory tract. They play a central role in the innate response to infection but may also modulate excessive inflammation. Both macrophages and ciliated epithelial cells respond to infection by releasing soluble mediators, leading to the recruitment of innate and adaptive effector cells. To study the role of lung macrophages in acute respiratory viral infection, we depleted them by the inhalation of clodronate liposomes in an established mouse model of respiratory syncytial virus (RSV) disease. Infection caused an immediate local release of inflammatory cytokines and chemokines, peaking on day 1, which was virtually abolished by clodronate liposome treatment. Macrophage depletion inhibited the activation (days 1 to 2) and recruitment (day 4) of natural killer (NK) cells and enhanced peak viral load in the lung (day 4). However, macrophage depletion did not affect the recruitment of activated CD4 or CD8 T cells, weight loss, or virus-induced changes in lung function. Therefore, lung macrophages play a central role in the early responses to viral infection but have remarkably little effect on the adaptive response occurring at the time of peak disease severity.
authors.affiliation: Department of Respiratory Medicine, Paddington Campus of Imperial College, Norfolk Place, London W2 1PG, United Kingdom. p.openshaw@imperial.ac.uk
authors.forename: Philippa K
authors.initials: PK
authors.lastname: Pribul
authors.forename: James
authors.initials: J
authors.lastname: Harker
authors.forename: Belinda
authors.initials: B
authors.lastname: Wang
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.forename: John S
authors.initials: JS
authors.lastname: Tregoning
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schwarze
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Openshaw
mesh_terms: D000818:Animals; D018925:Chemokines; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D018450:Disease Progression; D008214:Lymphocytes / Q000378:metabolism / Q000821:virology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D013997:Time Factors; D019562:Viral Load
chemical_list: D018925:Chemokines; D016207:Cytokines; D004002:Clodronic Acid