title: Differential capacity for complement receptor-mediated immune evasion by Porphyromonas gingivalis depending on the type of innate leukocyte.
abstract: The complement system plays a central role in immunity and inflammation, although certain pathogens can exploit complement to undermine protective immunity. In this context, the periodontal keystone pathogen Porphyromonas gingivalis was previously shown by our group to evade killing by neutrophils or macrophages through exploitation of complement C5a receptor 1 (C5aR1) and complement receptor 3 (CR3). Here, we examined whether P. gingivalis uses complement receptors to also subvert killing by dendritic cells. In line with earlier independent studies, intracellular viable P. gingivalis bacteria could be recovered from mouse bone-marrow-derived dendritic cells (BMDC) or human monocyte-derived dendritic cells (MDDC) exposed to the pathogen. However, in the presence of C5a, the intracellular survival of P. gingivalis was significantly decreased in a C5aR1-dependent way. Further work using wild-type and receptor-knockout BMDC showed that, in the presence of C3a, the C3a receptor (C3aR) similarly enhanced the intracellular killing of P. gingivalis. In contrast, C5aR2, an alternative receptor for C5a (G protein-coupled receptor 77), was associated with increased intracellular P. gingivalis viable counts, consistent with the notion that C5aR2 functions as a negative regulator of C5aR1 activity. Moreover, P. gingivalis failed to use CR3 as a phagocytic receptor in BMDC, in contrast to our earlier findings in macrophages where CR3-mediated uptake promotes P. gingivalis survival. Collectively, these data show that complement receptors mediate cell-type-specific effects on how innate leukocytes handle P. gingivalis, which appears to exploit complement to preferentially evade those cells (neutrophils and macrophages) that are most often encountered in its predominant niche, the periodontal pocket.
authors.affiliation: Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Hajishengallis
authors.affiliation: Department of Oral Immunology and Infectious Diseases, University of Louisville, Louisville, KY, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Krauss
authors.affiliation: Department of Oral Immunology and Infectious Diseases, University of Louisville, Louisville, KY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Jotwani
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Lambris
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D010861:Fimbriae, Bacterial / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D007962:Leukocytes / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000472:pathogenicity; D011951:Receptors, Complement / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement
keywords: 
  Porphyromonas gingivalis
  ; C3aR; C5aR1; C5aR2; CR3; Complement; dendritic cells; immune evasion; intracellular killing