TY - JOUR

T1 - The atherogenic bacterium Porphyromonas gingivalis evades circulating phagocytes by adhering to erythrocytes

AU - Belstrøm, Daniel

AU - Holmstrup, Palle

AU - Damgaard, Christian

AU - Borch, Tanja S

AU - Skjødt, Mikkel-Ole

AU - Bendtzen, Klaus

AU - Nielsen, Claus H

PY - 2011/4/1

Y1 - 2011/4/1

N2 - A relationship between periodontitis and coronary heart disease has been investigated intensively. A pathogenic role for the oral bacterium Porphyromonas gingivalis has been suggested for both diseases. We examined whether complement activation by P. gingivalis strain ATCC 33277 allows the bacterium to adhere to human red blood cells (RBCs) and thereby evade attack by circulating phagocytes. On incubation with normal human serum, the P. gingivalis strain efficiently fixed complement component 3 (C3). Incubation of bacteria with washed whole blood cells suspended in autologous serum resulted in a dose- and time-dependent adherence to RBCs. The adherence required functionally intact complement receptor 1 (CR1; also called CD35) on the RBCs and significantly inhibited the uptake of P. gingivalis by neutrophils and B cells within 1 min of incubation (by 64% and 51%, respectively) and that by monocytes after between 15 min and 30 min of incubation (by 66% and 53%, respectively). The attachment of C3b/iC3b to bacterium-bearing RBCs decreased progressively after 15 min, indicating that conversion of C3 fragments into C3dg occurred, decreasing the affinity for CR1 on RBCs. We propose that P. gingivalis exploits RBCs as a transport vehicle, rendering it inaccessible to attack by phagocytes, and by doing so plays a role in the development of systemic diseases.

AB - A relationship between periodontitis and coronary heart disease has been investigated intensively. A pathogenic role for the oral bacterium Porphyromonas gingivalis has been suggested for both diseases. We examined whether complement activation by P. gingivalis strain ATCC 33277 allows the bacterium to adhere to human red blood cells (RBCs) and thereby evade attack by circulating phagocytes. On incubation with normal human serum, the P. gingivalis strain efficiently fixed complement component 3 (C3). Incubation of bacteria with washed whole blood cells suspended in autologous serum resulted in a dose- and time-dependent adherence to RBCs. The adherence required functionally intact complement receptor 1 (CR1; also called CD35) on the RBCs and significantly inhibited the uptake of P. gingivalis by neutrophils and B cells within 1 min of incubation (by 64% and 51%, respectively) and that by monocytes after between 15 min and 30 min of incubation (by 66% and 53%, respectively). The attachment of C3b/iC3b to bacterium-bearing RBCs decreased progressively after 15 min, indicating that conversion of C3 fragments into C3dg occurred, decreasing the affinity for CR1 on RBCs. We propose that P. gingivalis exploits RBCs as a transport vehicle, rendering it inaccessible to attack by phagocytes, and by doing so plays a role in the development of systemic diseases.

KW - Adolescent

KW - Adult

KW - Aged

KW - Atherosclerosis

KW - Bacterial Adhesion

KW - Cell Adhesion

KW - Cell Separation

KW - Complement Activation

KW - Complement C3

KW - Erythrocytes

KW - Female

KW - Flow Cytometry

KW - Humans

KW - Male

KW - Middle Aged

KW - Phagocytes

KW - Porphyromonas gingivalis

KW - Young Adult

U2 - 10.1128/IAI.01036-10

DO - 10.1128/IAI.01036-10

M3 - Journal article

C2 - 21245264

VL - 79

SP - 1559

EP - 1565

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 4

ER -