Scavenger Receptors SR-AI/II and MARCO limit pulmonary dendritic cell migration and allergic airway inflammation.
The class A scavenger receptors (SR-A) MARCO and SR-AI/II are expressed on lung macrophages (MPhis) and dendritic cells (DCs) and function in innate defenses against inhaled pathogens and particles. Increased expression of SR-As in the lungs of mice in an OVA-asthma model suggested an additional role in modulating responses to an inhaled allergen. After OVA sensitization and aerosol challenge, SR-AI/II and MARCO-deficient mice exhibited greater eosinophilic airway inflammation and airway hyperresponsiveness compared with wild-type mice. A role for simple SR-A-mediated Ag clearance ("scavenging") by lung MPhis was excluded by the observation of a comparable uptake of fluorescent OVA by wild-type and SR-A-deficient lung MPhis and DCs. In contrast, airway instillation of fluorescent Ag revealed a significantly higher traffic of labeled DCs to thoracic lymph nodes in SR-A-deficient mice than in controls. The increased migration of SR-A-deficient DCs was accompanied by the enhanced proliferation in thoracic lymph nodes of adoptively transferred OVA-specific T cells after airway OVA challenge. The data identify a novel role for SR-As expressed on lung DCs in the down-regulation of specific immune responses to aeroallergens by the reduction of DC migration from the site of Ag uptake to the draining lymph nodes.
Arredouani
Mohamed S
MS
Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
Franco
Francesca
F
Imrich
Amy
A
Fedulov
Alexey
A
Lu
Xin
X
Perkins
David
D
Soininen
Raija
R
Tryggvason
Karl
K
Shapiro
Steven D
SD
Kobzik
Lester
L
D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D015870:Gene Expression; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
C092228:Marco protein, mouse; D011971:Receptors, Immunologic; D051117:Scavenger Receptors, Class A; D010047:Ovalbumin