Contrasting roles of macrophages and dendritic cells in controlling initial pulmonary Brucella infection.
Control of pulmonary pathogens constitutes a challenging task as successful immune responses need to be mounted without damaging the lung parenchyma. Using immunofluorescence microscopy and flow cytometry, we analyzed in the mouse the initial innate immune response that follows intranasal inoculation of Brucella abortus. Bacteria were absent from parenchymal dendritic cells (DC) but present in alveolar macrophages in which they replicated. When the number of alveolar macrophages was reduced prior to Brucella infection, small numbers of pulmonary DC were infected and a massive recruitment of TNF-α- and iNOS-producing DC ensued. Coincidentally, Brucella disseminated to the lung-draining mediastinal lymph nodes (LN) where they replicated in both migratory DC and migratory alveolar macrophages. Together, these results demonstrate that alveolar macrophages are critical regulators of the initial innate immune response against Brucella within the lungs and show that pulmonary DC and alveolar macrophages play rather distinct roles in the control of microbial burden.
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Marseille, France.
Cristel
C
Archambaud
Suzana P
SP
Salcedo
Hugues
H
Lelouard
Elisabeth
E
Devilard
Beatrice
B
de Bovis
Nico
N
Van Rooijen
Jean-Pierre
JP
Gorvel
Bernard
B
Malissen
D000818:Animals; D058491:Bacterial Load; D002003:Brucella abortus / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D002006:Brucellosis / Q000276:immunology* / Q000382:microbiology / Q000635:transmission; D002452:Cell Count; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology* / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II