Immune complex-dependent remodeling of the airway vasculature in response to a chronic bacterial infection.
Chronic inflammation in the airways is associated with dramatic architectural changes in the walls of the airways and in the vasculature they contain. In this study, we show that the adaptive immune system is essential for airway remodeling that occurs in mice that are chronically infected with the respiratory pathogen Mycoplasma pulmonis. Angiogenesis, lymphangiogenesis, and epithelial remodeling were greatly reduced in mice that lacked B cells. Substantiating a role for Ab and airway immune complexes, we found that the transfer of immune serum to B cell-deficient mice could reconstitute pathogen-induced angiogenesis. Inflammatory cells recruited to the infected airways were activated by the humoral response, and this activation correlated with the induction of genes for remodeling factors such as vascular endothelial growth factor-D. The results reveal a novel pathway whereby T cell-dependent humoral immunity to a persistent airway infection can induce inflammation-dependent angiogenesis, lymphangiogenesis, and chronic airway pathology.
Aurora
Arin B
AB
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA.
Baluk
Peter
P
Zhang
DongJi
D
Sidhu
Sukhvinder S
SS
Dolganov
Gregory M
GM
Basbaum
Carol
C
McDonald
Donald M
DM
Killeen
Nigel
N
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000473:pathology; D007700:Kinetics; D042583:Lymphangiogenesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009175:Mycoplasma Infections / Q000276:immunology* / Q000473:pathology*; D045803:Mycoplasma pulmonis / Q000276:immunology / Q000472:pathogenicity; D009389:Neovascularization, Pathologic; D012137:Respiratory System / Q000098:blood supply* / Q000276:immunology* / Q000473:pathology; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000473:pathology*
D000907:Antibodies, Bacterial; D000936:Antigen-Antibody Complex