Lymphoid Tissue–Resident Alcaligenes Establish an Intracellular Symbiotic Environment by Creating a Unique Energy Shift in Dendritic Cells

Abstract

Lymphoid-tissue-resident commensal bacteria (LRCs), including Alcaligenes faecalis, are present in intestinal lymphoid tissue including the Peyer's patches (PPs) of mammals and modulate the host immune system. Although LRCs can colonize within dendritic cells (DCs), the mechanisms through which LRCs persist in DCs and the symbiotic relationships between LRCs and DCs remain to be investigated. Here, we show an intracellular symbiotic system in which the LRC Alcaligenes creates a unique energy shift in DCs. Whereas DCs showed low mitochondrial respiration when they were co-cultured with Escherichia coli, DCs carrying A. faecalis maintained increased mitochondrial respiration. Furthermore, E. coli induced apoptosis of DCs but A. faecalis did not. Regarding an underlying mechanism, A. faecalis-unlike E. coli-did not induce intracellular nitric oxide (NO) production in DCs due to the low activity of its lipopolysaccharide (LPS). Therefore, A. faecalis, an example of LRCs, may persist within intestinal lymphoid tissue because they elicit little NO production in DCs. In addition, the symbiotic DCs exhibit characteristic physiologic changes, including a low rate of apoptosis and increased mitochondrial respiration.

Lipopolysaccharide Derived From the Lymphoid-Resident Commensal Bacteria Alcaligenes faecalis Functions as an Effective Nasal Adjuvant to Augment IgA Antibody and Th17 Cell Responses

“…We also found that the levels of IL-5 and TNF-α production from T cells in the CT group were elevated but not in Alcaligenes LPS group. Consistent with this result, our previous studies showed that the production levels of TNF-α and nitric oxide (NO), an inflammatory molecule that induces TNF-α production, were lower in BMDCs treated with Alcaligenes LPS than in BMDCs treated with E. coli LPS ( 6 , 36 ). IL-5 induces the differentiation of eosinophils ( 37 ) and interacts with IL-17 to promote the survival and degranulation of eosinophils, leading to tissue inflammation and damage ( 38 ).…”

“…Indeed, compared with E. coli LPS, Alcaligenes LPS showed lower endotoxin activity in the limulus amebocyte lysate test and caused only limited inflammatory reactions when intraperitoneally injected into mice, including lower levels of serum IL-6, less change in body temperature, and less damage to lung tissue with little infiltration of inflammatory cells, such as neutrophils and eosinophils ( 6 ). In addition, unlike E. coli LPS, Alcaligenes LPS showed little activity to induce apoptosis when co-cultured with BMDCs ( 36 ). In terms of IL-6 production from BMDCs, TLR4-deficient BMDCs did not respond to Alcaligenes LPS, whereas TLR2-deficient BMDCs produced comparable levels of IL-6 as wild type BMDCs ( 6 ).…”

Nutritional Components in Western Diet Versus Mediterranean Diet at the Gut Microbiota–Immune System Interplay. Implications for Health and Disease

“…Alcaligenes are opportunistic bacteria residing in the GALTs, similar to those in the Peyer’s patch, where DCs recognize their LPS through TLR-4 activation to foster the activity of IL-6 and IgA production [ 109 ]. Regardless of the fact that the systemic presence of LPS in the bloodstream (endotoxemia) is related with chronic inflammation [ 110 ], the presence of Alcaligenes in the GALT means that LPS interacts symbiotically with DCs in healthy individuals [ 111 ]. In addition, other bacteria, such as Clostridia, are a class of bacteria belonging to the phylum Firmicutes, and clusters IV and XIVa represent an important part of the healthy gut microbiota (10-40%), with important implications for the host [ 112 ].…”

Lipid A-Mediated Bacterial–Host Chemical Ecology: Synthetic Research of Bacterial Lipid As and Their Development as Adjuvants

“…A. faecalis LPS would participate in the vigilance of the host’s immune system through the production of IgA, which in turn may promote the survival of symbiotic bacteria in PPs [ 58 ]. The extracted A. faecalis LPS fraction has a lower potency to induce inflammation, nitric oxide, and apoptosis than E. coli LPS, suggesting that these functions would also contribute to establishing symbiotic relationships with the host [ 7 , 59 ].…”