Impact of Fusobacterium nucleatum in the gastrointestinal tract on natural killer cells

Figure 1 Effects of Fusobacteriumnucleatum, Peptostreptococcusanaerobius, and Parvimonasmicra on natural killer cells in vitro. Natural killer 92 cells were cultured for 24 or 48 h with each organism at a multiplicity of infection of 100:1, 250:1 or 500:1. Post-incubation, viability in the cultures was assessed using trypan blue staining. A: Fusobacterium nucleatum; B: Peptostreptococcus anaerobius; C: Parvimonas micra. F. nucleatum: Fusobacterium nucleatum; P. anaerobius: Peptostreptococcus anaerobius; P. micra: Parvimonas micra.

Figure 2 Experimental design. A: Mice were divided into four goups: Control, anti-control (antibiotics only), phosphate-buffered saline (PBS) (PBS after antibiotics), and Fusobacterium nucleatum (F. nucleatum) (F. nucleatum after antibiotics). The mice were treated with broad-spectrum antibiotics for 3 wk (except control), F. nucleatum was introduced to mice every 2 d for 6 wk by oral gavage; B: After treatments, the levels of total gut bacteria (left) and F. nucleatum (right) were evaluated; C: After administration of F. nucleatum, levels of total bacteria (left) and F. nucleatum (right) in mice were again evaluated. Data are expressed as means ± SD of three independent experiments. PBS: Phosphate-buffered saline.

Figure 3 Body weight, colon length, and mucosal surface among the experimental groups. A: Weights of mice; B: Colon length and mucosal surface. PBS: Phosphate-buffered saline; FN: F. nucleatum.

Figure 4 Blood levels of interferon-gamma. To indirectly evaluate the activity of natural killer cells, whole blood from each mouse was collected at necropsy and levels of interferon-gamma evaluated by ELISA. Data are expressed as means ± SD of three independent experiments. Value significantly different at ^aP < 0.05. IFN-γ: Interferon-gamma; PBS: Phosphate-buffered saline; FN: F. nucleatum.

Figure 5 Intestinal levels of CD3 and NKp46 cells. A: CD3⁺ cells; B: NKp46⁺ cells. Data are expressed as means ± SD of three independent experiments. Value significantly different at ^aP < 0.05. NK: Natural killer; PBS: Phosphate-buffered saline; FN: F. nucleatum.

Figure 6 Plasma pro-inflammatory cytokine levels. A: Interleukin (IL)-1β; B: Tumor necrosis factor-α; C: IL-6; D: IL-18; E: IL-12p70. Data are expressed as means ± SD of three independent experiments. Value significantly different at ^aP < 0.05. PBS: Phosphate-buffered saline; FN: F. nucleatum; IL: Interleukin; TNF-α: Tumor necrosis factor-α.

Figure 7 A possible mechanism. High levels of F. nucleatum in the gastrointestinal tract induce an increase in plasma pro-inflammatory cytokines, which reduces natural killer cell activity. IL: Interleukin; TNF-α: Tumor necrosis factor-α; NK: Natural killer.