CCR5 mediates pro-osteoclastic and osteoclastogenic leukocyte chemoattraction.
Periodontal disease (PD) progression involves the selective leukocyte infiltration into periodontium, supposedly mediated by the chemokine/chemokine receptor system. In this study, we investigated the role of chemokine receptor CCR5 in the immunoregulation of experimental PD in C57BL/6 (WT) and CCR5KO mice. Aggregatibacter actinomycetem comitans infection triggered the chemoattraction of distinct CCR5+ leukocyte subpopulations (determined by flow cytometry): CCR5+F4/80+ leukocytes, which co-express CD14 , CCR2, TNF-α, and IL-1β, indicative of activated macrophages; and CCR5+CD4+ cells, which co-express CXCR3, IFN-γ, and RANKL, indicative of Th1 lymphocytes, therefore comprising pro-osteoclastic and osteoclastogenic cell subsets, respectively. CCR5KO mice presented a lower PD severity (lower inflammation and alveolar bone loss) when compared with the WT strain, since the migration of F4/80+, TNF-α+, CD4+, and RANKL+ cells specifically decreased due to the lack of CCR5. Also, ELISA analysis demonstrated that the production of TNF-α, IL-1β, IL-6, IFN-γ, and RANKL in periodontal tissues was significantly decreased in the CCR5KO strain. The periodontal bacterial load and antimicrobial patterns were unaltered in CCR5KO mice. Our results demonstrate that the chemokine receptor is involved in the migration of distinct leukocyte subpopulations throughout experimental PD, being a potential target for therapeutic intervention in PD.
OSTEOimmunology lab, Department of Biological Sciences, School of Dentistry of Bauru, São Paulo University-FOB/USP, Al. Octávio Pinheiro Brisola, 9-75-CEP 17012-901, Bauru, SP, Brazil.
S B
SB
Ferreira
C E
CE
Repeke
F M
FM
Raimundo
I S
IS
Nunes
M J
MJ
Avila-Campos
B R
BR
Ferreira
J
J
Santana da Silva
A P
AP
Campanelli
G P
GP
Garlet
D016976:Aggregatibacter actinomycetemcomitans / Q000502:physiology; D016301:Alveolar Bone Loss / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D058491:Bacterial Load; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D055113:Chronic Periodontitis / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000276:immunology*; D053245:RANK Ligand / Q000096:biosynthesis; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
D016207:Cytokines; D053245:RANK Ligand; D019713:Receptors, CCR5; D007371:Interferon-gamma