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Strain-dependent induction of cytokine profiles in the gut by orally administered Lactobacillus strains

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Author: Maassen, C.B.M. · Holten-Neelen, C. van · Balk, F. · Bak-Glashouwer, M.-J.H. den · Leer, R.J. · Laman, J.D. · Boersma, W.J.A. · Claassen, E.
Source:Vaccine, 18, 2613-2623
Identifier: 71917
Keywords: Immunohistochemistry · Mucosal immune response · Probiotic · adjuvant · cytokine · gamma interferon · immunoglobulin A · interleukin 10 · interleukin 1alpha · interleukin 1beta · interleukin 2 · interleukin 4 · probiotic agent · tumor necrosis factor alpha · animal experiment · animal model · antibody response · article · controlled study · cytokine production · enzyme linked immunosorbent assay · female · humoral immunity · immune response · immunohistochemistry · intestine mucosa · Lactobacillus · Lactobacillus brevis · Lactobacillus casei · Lactobacillus fermentum · Lactobacillus plantarum · Lactobacillus reuteri · mouse · mucosa · nonhuman · priority journal · Adjuvants, Immunologic · Administration, Oral · Animals · Chickens · Chikungunya virus · Cytokines · Duodenum · Female · Food Microbiology · gamma-Globulins · Haptens · Injections, Intraperitoneal · Interleukin-2 · Intestinal Mucosa · Lactobacillus · Lactobacillus casei · Mice · Mice, Inbred BALB C · Microvilli · Peyer's Patches · Species Specificity · Th2 Cells · Viral Vaccines


Different Lactobacillus strains are frequently used in consumer food products. In addition, recombinant lactobacilli which contain novel expression vectors can now be used in immunotherapeutic applications such as oral vaccination strategies and in T cell tolerance induction approaches for autoimmune disease. Both for food and clinical applications of lactobacilli, proper selection of wild type strains is crucial.For that purpose, eight different common Lactobacillus strains were analysed with respect to mucosal induction of pro- and anti-inflammatory cytokines, IgA-producing plasma cells in the gut, as well as systemic antibody responses against a parenterally administered antigen. Immunohistochemical analysis of cytokine-producing cells in the gut villi showed no significant induction of the cytokines IL-1α, IFN-γ, IL-4 or IL-10 after oral administration of wild type Lactobacillus strains. In contrast, oral administration of L. reuteri and L. brevis induced expression of the proinflammatory/Th1 cytokines TNF-α, IL-2 and/or IL-1β. Oral administration of these two strains and L. fermentum also significantly enhanced the IgG response against parenterally administered haptenated chicken gamma globulin (TNP-CGG). The five other strains did not show this adjuvanticity. L. reuteri induced relatively high levels of IgG2a compared to L. murines, a nonadjuving Lactobacillus strain.These findings imply that different Lactobacillus strains induce distinct mucosal cytokine profiles and possess differential intrinsic adjuvanticity. This suggests that rational Lactobacillus strain selection provides a strategy to influence cytokine expression and thereby influence immune responses. Copyright (C) 2000 Elsevier Science Ltd