Outer membrane protein A renders dendritic cells and macrophages responsive to CCL21 and triggers dendritic cell migration to secondary lymphoid organs.
Outer membrane protein A (OmpA) is a class of bacterial cell wall protein that is immunogenic without adjuvant. As specific immune responses are initiated in the lymph nodes (LN, we analyzed the effect of the OmpA from Klebsiella pneumoniae (KpOmpA) onchemokine/ chemokine receptor expression by APC and on cell migration to the LN. Upon contact with KpOmpA, human immature DC and macrophages acquire CCR7 expression and responsiveness to CCL21. In parallel, CCR1 and CCR5 expression is down-regulated and CXCL8, CCL2, CCL3 and CCL5 production is up-regulated. Mice injected subcutaneously with KpOmpA present a transient inflammatory reaction at the site of injection accompanied by an enlargement of the draining LN with a higher proportion of DC and macrophages. Lastly, when exposed to KpOmpA prior injection, DC but not macrophages migrate to the draining LN. In conclusion, KpOmpA confers a migratory phenotype to DC and triggers their migration to the regional LN. This property contributes to explain how innate cells initiate adaptive immune response upon recognition of conserved bacterial components and also why OmpA is immunogenic in the absence of adjuvant.
Jeannin
Pascale
P
Centre d'Immunologie Pierre Fabre, Saint-Julien en Genevois, France. pascale.jeannin@pierre-fabre.com
Magistrelli
Giovanni
G
Herbault
Nathalie
N
Goetsch
Liliane
L
Godefroy
Sylvie
S
Charbonnier
Peggy
P
Gonzalez
Alexandra
A
Delneste
Yves
Y
D019264:Adoptive Transfer; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000235:genetics; D019742:Chemokines, CC / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000473:pathology; D008221:Lymphoid Tissue / Q000166:cytology*; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D054389:Receptors, CCR1; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000235:genetics; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515300:CCR1 protein, human; C515370:CCR7 protein, human; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; C515301:Ccr1 protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D016209:Interleukin-8; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D008565:Membrane Proteins; D054389:Receptors, CCR1; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; C078167:OMPA outer membrane proteins