title: Unprimed, M1 and M2 Macrophages Differentially Interact with Porphyromonas gingivalis.
abstract: Porphyromonas gingivalis is a keystone pathogen in the development of chronic periodontitis. Tissue macrophages are amongst the first immune cells to respond to bacteria and depending on the cytokine profile at the infection site, macrophages are primed to react to infection in different ways. Priming of naive macrophages with IFN-γ produces a classical pro-inflammatory, antibacterial M1 macrophage after TLR ligation, whereas priming with IL-4 induces an anti-inflammatory tissue-repair M2 phenotype. Previous work has shown that M1 are preferentially generated in gingival tissue following infection with P. gingivalis. However, few studies have investigated the interactions of macrophage subsets with P. gingivalis cells. The aim of this study was to determine the ability of naive, M1 and M2 macrophages to phagocytose P. gingivalis and investigate how this interaction affects both the bacterial cell and the macrophage. M1 and M2 macrophages were both found to have enhanced phagocytic capacity compared with that of naive macrophages, however only the naive and M1 macrophages were able to produce a respiratory burst in order to clear the bacteria from the phagosome. P. gingivalis was found to persist in naive and M2, but not M1 macrophages for 24 hours. Phagocytosis of P. gingivalis also induced high levels of TNF-α, IL-12 and iNOS in M1 macrophages, but not in naive or M2 macrophages. Furthermore, infection of macrophages with P. gingivalis at high bacteria to macrophage ratios, while inducing an inflammatory response, was also found to be deleterious to macrophage longevity, with high levels of apoptotic cell death found in macrophages after infection. The activation of M1 macrophages observed in this study may contribute to the initiation and maintenance of a pro-inflammatory state during chronic periodontitis.
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, Australia.
authors.forename: Roselind S
authors.initials: RS
authors.lastname: Lam
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, Australia.
authors.forename: Neil M
authors.initials: NM
authors.lastname: O'Brien-Simpson
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, Australia.
authors.forename: James A
authors.initials: JA
authors.lastname: Holden
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, Australia.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Lenzo
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, Australia.
authors.forename: Shao B
authors.initials: SB
authors.lastname: Fong
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, Australia.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Reynolds
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002460:Cell Line; D015870:Gene Expression / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000145:classification / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D050296:Microbial Viability / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D010588:Phagosomes / Q000276:immunology / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology
chemical_list: D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II