Abstract
The prevalence of inflammatory bowel disease (IBD) has increased in Western countries during the course of the twentieth century, and is evolving to be a global disease. Recently we showed that a bacterial meal of a non-commensal, non-pathogenic methanotrophic soil bacterium, Methylococcus capsulatus Bath prevents experimentally induced colitis in a murine model of IBD. The mechanism behind the effect has this far not been identified. Here, for the first time we show that M. capsulatus, a soil bacterium adheres specifically to human dendritic cells, influencing DC maturation, cytokine production, and subsequent T cell activation, proliferation and differentiation. We characterize the immune modulatory properties of M. capsulatus and compare its immunological properties to those of another Gram-negative gammaproteobacterium, the commensal Escherichia coli K12, and the immune modulatory Gram-positive probiotic bacterium, Lactobacillus rhamnosus GG in vitro. M. capsulatus induces intermediate phenotypic and functional DC maturation. In a mixed lymphocyte reaction M. capsulatus-primed monocyte-derived dendritic cells (MoDCs) enhance T cell expression of CD25, the γ-chain of the high affinity IL-2 receptor, supports cell proliferation, and induce a T cell cytokine profile different from both E. coli K12 and Lactobacillus rhamnosus GG. M. capsulatus Bath thus interacts specifically with MoDC, affecting MoDC maturation, cytokine profile, and subsequent MoDC directed T cell polarization.
Highlights
Microbes are associated with all epithelial surfaces of animal hosts, the highest number, and most diverse microbial populations are found in the intestines
To determine whether the target cells were dendritic cells (DCs) we incubated M. capsulatus Bath with CD14+ monocytes or monocyte-derived dendritic cells (MoDCs) generated from CD14+ monocytes in the presence of IL-4 and GM-CSF
The interaction between M. capsulatus Bath and MoDCs was further visualized by scanning electron microscopy (SEM) showing M. capsulatus Bath in large clusters on MoDCs after 3 h of co-incubation, even after several washes with PBS (Figure 1D)
Summary
Microbes are associated with all epithelial surfaces of animal hosts, the highest number, and most diverse microbial populations are found in the intestines. Some 10–100 trillion microbes colonizes the human gastrointestinal tract, with the highest numbers present in the colon (Turnbaugh et al, 2007). The physiology of these microbes and their hosts is closely connected and mutually regulated (Brown et al, 2013). The host must maintain a mutualistic relationship with the commensal microbiome, while retaining protective responsiveness against pathogenic bacteria. To achieve this it must preserve epithelial integrity and regulate pro- and anti-inflammatory signaling, in an appropriate manner. Homeostasis is maintained through continuous and dynamic interactions and communication between the intestinal microbiota, the epithelium, and immune cells in the intestinal mucosa
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