Mice lacking monocyte chemoattractant protein 1 have enhanced susceptibility to an interstitial polymicrobial infection due to impaired monocyte recruitment.
Monocyte chemoattractant protein 1 (MCP-1) is an important chemokine that induces monocyte recruitment in a number of different pathologies, including infection. To investigate the role of MCP-1 in protecting a host from a chronic interstitial polymicrobial infection, dental pulps of MCP-1(-/-) mice and controls were inoculated with six different oral pathogens. In this model the recruitment of leukocytes and the impact of a genetic deletion on the susceptibility to infection can be accurately assessed by measuring the progression of soft tissue necrosis and osteolytic lesion formation. The absence of MCP-1 significantly impaired the recruitment of monocytes, which at later time points was threefold higher in the wild-type mice than in MCP-1(-/-) mice (P < 0.05). The consequence was significantly enhanced rates of soft tissue necrosis and bone resorption (P < 0.05). We also determined that the MCP-1(-/-) mice were able to recruit polymorphonuclear leukocytes (PMNs) to a similar or greater extent as controls and to produce equivalent levels of Porphyromonas gingivalis-specific total immunoglobulin G (IgG) and IgG1. These results point to the importance of MCP-1 expression and monocyte recruitment in antibacterial defense and demonstrate that antibacterial defense is not due to an indirect effect on PMN recruitment or modulation of the adaptive immune response.
Chae
P
P
Department of Endodontics, Boston University School of Dental Medicine, Massachusetts 02118, USA.
Im
M
M
Gibson
F
F
Jiang
Y
Y
Graves
D T
DT
D000818:Animals; D016866:Bacteroidaceae Infections / Q000276:immunology / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology*; D003782:Dental Pulp / Q000382:microbiology / Q000473:pathology; D004198:Disease Susceptibility / Q000276:immunology; D005674:Fusobacterium Infections / Q000276:immunology / Q000473:pathology; D016967:Fusobacterium nucleatum / Q000276:immunology; D016908:Gram-Positive Bacterial Infections / Q000276:immunology / Q000473:pathology; D007958:Leukocyte Count; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D010462:Peptostreptococcus / Q000276:immunology; D016966:Porphyromonas gingivalis / Q000276:immunology; D018713:Prevotella intermedia / Q000276:immunology; D013290:Streptococcal Infections / Q000276:immunology / Q000473:pathology; D013291:Streptococcus / Q000276:immunology; D013295:Streptococcus mutans / Q000276:immunology
D018932:Chemokine CCL2