Lactobacilli from human gastrointestinal mucosa are strong stimulators of IL-12 production

Abstract

SUMMARYInteraction of macrophages with bacteria is a stimulus for production of cytokines such as IL-10 and IL-12. IL-12 stimulates T cell and natural killer (NK) cell cytotoxicity and interferon-gamma (IFN-g) production. IL-10 opposes the T cell-stimulating action of IL-12, decreases the release of proinflammatory cytokines from macrophages, and stimulates B cells. We have studied the capacity of human intestinal isolates from the three Lactobacillus species dominating on the human gastrointestinal mucosa, L. plantarum, L. rhamnosus and L. paracasei ssp. paracasei, to induce production of IL-10 and IL-12 from human blood mononuclear cells, or monocytes. Whole killed lactobacilli were potent stimulators of IL-12 over a wide range of bacterial concentrations. Lactobacillus paracasei gave the highest levels of IL-12 (1·5 ng/ml in response to 5 × 10 6 bacteria/ml), roughly 10 times more than obtained by stimulation with L. rhamnosus or L. plantarum. Escherichia coli induced on average < 50 pg/ml of IL-12 regardless of the bacterial concentration used. The secretion of free p40 subunit IL-12 followed the same pattern as the secretion of p70 (bioactive IL-12) with regard to the efficiency of different bacteria as stimulators. Escherichia coli was the most efficient trigger of IL-10 production, inducing 0·5 ng/ml IL-10 after stimulation with 5 × 10 6 bacteria/ml. Lactobacillus rhamnosus induced the highest levels of IL-10 among the lactobacilli (0·5 ng/ml) compared with 0·1 ng/ml evoked by L. plantarum or L. paracasei, but 10 times more bacteria were required for optimal stimulation than with E. coli. When neutralizing anti-IL-10 antibodies were added to the cultures, the IL-12-inducing capacity of L. rhamnosus was increased markedly, while that of E. coli remained low. The results show that mucosa-associated lactobacilli can be potent stimulators of IL-12, and thus potentially of cell-mediated immunity, if they pass over the gut epithelial barrier and interact with cells of the gut immune system.

Genes involved in obesity: Adipocytes, brain and microflora

“…Indeed we, and others, showed that probiotics present distinct strainspecific immunomodulatory capacities in vitro (Hessle et al, 1999;Maassen et al, 2000;Mercenier et al, 2004) which can be closely correlated with their in vivo anti-inflammatory potential. Interestingly, the anti-inflammatory effects of lactobacilli observed after either oral or systemic administration (Foligne et al, 2005;Sheil et al, 2004), suggest that the protective mechanisms might involve regulatory-cell populations.…”

Enhancing immunity by dietary consumption of a probiotic lactic acid bacterium (Bifidobacterium lactis HN019): optimization and definition of cellular immune responses

“…While we can provide no further evidence here as to the molecular signalling mechanisms by which B. lactis is able to enhance cellular immunity, it is known that phagocytic cells are stimulated by direct contact with LAB and sub-cellular fractions of bacterial cell walls (Keller et al, 1994;Miettinen et al, 1996). Furthermore, recent studies have indicated that LAB also induce mononuclear leucocytes to secrete procellular immunity cytokines such as interleukin-12 and interleukin-18, both of which are potent stimulators of NK cell activity and interferon production (Miettenen et al, 1999;Hessle et al, 1999). It is therefore possible that immune enhancement in humans by dietary consumption of B. lactis is due primarily to stimulation of the inter-communicating cytokine network, which serves to drive the immune system toward a general enhancement of cellular immune function.…”

Enhanced antiinflammatory capacity of a Lactobacillus plantarum mutant synthesizing modified teichoic acids

“…Different factors have been reported to contribute to the protective function of gut microflora such as maintaining a physical barrier against colonization or invasion by pathogens, facilitating nutrient digestion and assimilation, and providing immunological surveillance signals at the gut mucosalumen interface (5). It is widely accepted that the intestinal microflora plays an important role in maintaining the health of the host and possesses immunomodulating capacities (6)(7)(8)(9)(10). Lactic acid bacteria (LAB) are normal inhabitants of the human gastrointestinal tract and are major components of the dominant flora in the small bowel.…”

“…We established that the in vivo protective effect of LAB in a murine 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced model of colitis is strain-specific (20,21). Several LAB strains were reported to exert in vitro stimulatory properties on cells of the innate immune system, including macrophages and natural killer cells, and to induce the production of both proinflammatory cytokines, such as TNF-␣ and IL-12, and the antiinflammatory IL-10 cytokine (6,7,10,22). Previous reports have suggested that Gram-positive bacteria tend to preferentially stimulate IL-12 secretion, whereas Gram-negative bacteria predominantly induce IL-10 from stimulated monocytes and macrophages (23).…”