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Review
. 2007 May;14(5):485-92.
doi: 10.1128/CVI.00406-06. Epub 2007 Mar 14.

Proposed model: mechanisms of immunomodulation induced by probiotic bacteria

C Maldonado Galdeano  1 , A de Moreno de LeBlanc, G Vinderola, M E Bibas Bonet, G Perdigón
Affiliations
Review

Proposed model: mechanisms of immunomodulation induced by probiotic bacteria

C Maldonado Galdeano et al. Clin Vaccine Immunol. 2007 May.
No abstract available

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Figures

FIG. 1.
FIG. 1.
Scanning electron micrograph showing the interaction of Lactobacillus helveticus R389 with intestinal epithelial cells (IEC) obtained from the small intestine of BALB/c mice. The epithelial cells were recovered from the small intestine after digestion with collagenase in adequate culture medium. A Lactobacillus helveticus suspension (1012 CFU/ml) was added to isolated IEC. After bacterial contact with IEC for 2 h, the samples were processed for scanning electron microscopy. Magnification, ×6,000.
FIG. 2.
FIG. 2.
Histological slices of intestine from BALB/c mice, showing the pathway of internalization to the gut by lactic acid bacteria. Animals received fluorescein isothiocyanate-labeled lactic acid bacteria (1 × 108 CFU/ml) by intragastric intubation. (A) Fluorescence in Peyer's patches of the small intestine of mice 5 min after administration of labeled Lactobacillus delbrueckii subsp. bulgaricus CRL 423 (isolated from yogurt). (B) Fluorescence in lamina propria of the small intestine of mice that received labeled Lactobacillus casei CRL 431 isolated from human feces. The samples were processed after 5 min of lactobacillus administration. (C) Fluorescence in the nodule and crypts of the large intestine of mice 10 min after administration of labeled Lactobacillus acidophilus CRL 724 isolated from feces. Magnification, ×1,000.
FIG. 3.
FIG. 3.
The local immune response in the gut induced by the interaction between probiotic bacteria and the epithelial and immune cells associated with the lamina propria of the small intestine. Activation of the innate immune response is shown. There would be different pathways of internalization for the probiotic bacteria present in the lumen of the small intestine: an M cell (MC) is associated with the epithelium, and an epithelial cell (EC) and the interdigitant dendritic cells (DC) are able to sample bacteria. After the interaction with the epithelial cells, probiotic bacteria or their fragments are internalized. The first cells that would interact with them are the antigen-presenting cells (APC), macrophages, and/or dendritic cells associated with the lamina propria of the gut. The interaction with epithelial cells induces IL-6 release. Macrophages and dendritic cells phagocytose the probiotic bacteria or their fragments, and they are induced to produce cytokines such as TNF-α and IFN-γ, which increase epithelial cell stimulation and initiate the cross talk between all the associated immune cells. Mast cells would also be stimulated to produce IL-4. Other cytokines, such as IL-10 and IL-6, are also produced to enhance the cytokine network of signals. The ingested bacteria or their particles could also be eliminated by phagocytosis clearance. IL-6 would favor the clonal expansion of IgA B lymphocytes, increasing the number of IgA-producing cells and the passage of them to plasmatic cells in the lamina propria of the gut. IL-6 together with IL-4 and TGF-β (not determined in our studies) can induce the T-independent switch from IgM to IgA on the surface of B cells and can promote in this way an increase in the number of B cells that are IgA+ in the lamina propria of the gut. EC, intestinal epithelial cells; MQ, macrophages; TL, T lymphocytes; BL, B lymphocytes; MS, mast cells; PC, plasma cells.
FIG. 4.
FIG. 4.
Systemic immune response induced by probiotic bacteria after interaction with the immune cells of the Peyer's patches. In the Peyer's patches, the probiotic bacteria or their fragments are internalized by M cells or in a paracellular way through follicle-associated epithelial cells of the Peyer's patches. After that, the bacteria or their particles interact with the macrophages and dendritic cells, which are activated to produce cytokines. As consequence of the bacterial stimulation to the immune cells in this inductor site of the immune response, cytokine production is enhanced, as well is the switch from IgM to IgA B cells. IL-10, IL-6, IL-4, and TGF-β from immune cells could also promote this T-independent switch. Probiotic stimulation can induce the IgA cycle, increasing the number of IgA+ cells in mucosal sites distant to the intestine. The IgA+ cells migrate to the mesenteric lymphoid node and then via the thoracic duct to the circulation, arriving in the bronchus and mammary glands. The cytokines released by probiotic stimulation in Peyer's patches are the biological messengers of the complex network of signals that activate the systemic immune response. DC, dendritic cells; MQ, macrophages cells; APC, antigen-presenting cells; TL, T lymphocytes; BL, B lymphocytes.
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