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.
Highlights
Chronic periodontitis is an inflammatory disease of the supporting tissues of the teeth characterised by accumulation of immune cells in gingival tissues leading to bone resorption, PLOS ONE | DOI:10.1371/journal.pone.0158629 July 6, 2016M1 Macrophages Phagocytose and Kill P. gingivalis eventuating in tooth loss [1]
Macrophages primed with IL-4 phagocytosed significantly higher levels of bacteria compared with naive macrophages, significantly lower amounts compared with M1 macrophages
We have previously demonstrated that CD86(+) macrophages producing nitric oxide (M1) are the primary phenotype generated in the gingival tissue during an in vivo infection with P. gingivalis [23], to date no study had addressed the specific interactions of macrophage subsets with P. gingivalis cells
Summary
M1 Macrophages Phagocytose and Kill P. gingivalis eventuating in tooth loss [1]. It affects around 30α of adults and has been linked to a higher risk of certain systemic diseases such as cardiovascular, diabetes, respiratory infections, pancreatic cancer, spontaneous pre-term birth and pre-term low birth weight [2,3,4,5]. Porphyromonas gingivalis is one of the bacterial biofilm species isolated from subgingival plaque most strongly associated with clinical indicators of periodontitis, including increased pocket depth and bleeding on probing [6, 7]. The level of P. gingivalis in subgingival plaque above threshold levels (>10% of total bacterial load) has been shown to predict imminent disease progression in periodontitis patients [9]. The extracellular Arg- and Lys-specific cysteine proteinases, outer membrane vesicles and variation in lipopolysaccharides (LPS) structure have been reported to be some of P. gingivalis major virulence factors that can induce variable immune responses, leading to dysregulated immunity [10,11,12]
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