Alveolar epithelial type II cells activate alveolar macrophages and mitigate P. Aeruginosa infection.
Although alveolar epithelial type II cells (AECII) perform substantial roles in the maintenance of alveolar integrity, the extent of their contributions to immune defense is poorly understood. Here, we demonstrate that AECII activates alveolar macrophages (AM) functions, such as phagocytosis using a conditioned medium from AECII infected by P. aeruginosa. AECII-derived chemokine MCP-1, a monocyte chemoattractant protein, was identified as a main factor in enhancing AM function. We proposed that the enhanced immune potency of AECII may play a critical role in alleviation of bacterial propagation and pneumonia. The ability of phagocytosis and superoxide release by AM was reduced by MCP-1 neutralizing antibodies. Furthermore, MCP-1(-/-) mice showed an increased bacterial burden under PAO1 and PAK infection vs. wt littermates. AM from MCP-1(-/-) mice also demonstrated less superoxide and impaired phagocytosis over the controls. In addition, AECII conditioned medium increased the host defense of airway in MCP-1(-/-) mice through the activation of AM function. Mechanistically, we found that Lyn mediated NFkappaB activation led to increased gene expression and secretion of MCP-1. Consequently Lyn(-/-) mice had reduced MCP-1 secretion and resulted in a decrease in superoxide and phagocytosis by AM. Collectively, our data indicate that AECII may serve as an immune booster for fighting bacterial infections, particularly in severe immunocompromised conditions.
Kannan
Shibichakravarthy
S
Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, North Dakota, USA.
Huang
Huang
H
Seeger
Drew
D
Audet
Aaron
A
Chen
Yaoyu
Y
Huang
Canhua
C
Gao
Hongwei
H
Li
Shaoguang
S
Wu
Min
M
D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D017077:Culture Media, Conditioned; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D005260:Female; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D051381:Rats; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology; D019061:src-Family Kinases / Q000378:metabolism
D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D016328:NF-kappa B; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases