Mucosal co-application of lactic acid bacteria and allergen induces counter-regulatory immune responses in a murine model of birch pollen allergy

Repa, Andreas; Grangette, Corinne; Daniel, Catherine; Hochreiter, Romana; Hoffmann‐Sommergruber, Karin; Thalhamer, Josef; Kraft, Dietrich; Breiteneder, Heimo; Mercenier, Annick; Wiedermann, Ursula

doi:10.1016/s0264-410x(03)00528-0

Cited by 119 publications

(109 citation statements)

References 47 publications

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“…As previously observed with PBMCs, purified monocytes produce higher levels of IL-12 and TNF when they are cultured with the gram-positive organism L. plantarum than when they are cultured with the gram-negative organisms E. coli and V. parvula. Murine splenocytes, with a repertoire of cells similar to that found in human PBMCs, also produce higher levels of IL-12 in response to L. plantarum than in response to E. coli (33). We found that in contrast to monocytes, immature DCs are practically unresponsive to L. plantarum and B. adolescentis but produce high levels of IL-12, TNF, IL-6, and IL-10 in response to E. coli and V. parvula.…”

Section: Discussionsupporting

confidence: 61%

Pattern of Cytokine Responses to Gram-Positive and Gram-Negative Commensal Bacteria Is Profoundly Changed when Monocytes Differentiate into Dendritic Cells

Karlsson¹,

Larsson²,

Wold

et al. 2004

Infect Immun

120

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The normal gastrointestinal bacterial flora is crucial for the maturation of acquired immunity via effects on antigen-presenting cells (APCs). Here we investigated how two types of APCs, monocytes and dendritic cells (DCs), react to different bacterial strains typical of the commensal intestinal microflora. Purified human monocytes and monocyte-derived DCs were stimulated with UV-inactivated gram-positive (Lactobacillus plantarum and Bifidobacterium adolescentis) and gram-negative (Escherichia coli and Veillonella parvula) bacterial strains. Monocytes produced higher levels of interleukin 12p70 (IL-12p70) and tumor necrosis factor (TNF), as detected by an enzyme-linked immunosorbent assay, in response to L. plantarum than in response to E. coli and V. parvula. In contrast, DCs secreted large amounts of IL-12p70, TNF, IL-6, and IL-10 in response to E. coli and V. parvula but were practically unresponsive to L. plantarum and B. adolescentis. The lack of a response to the gram-positive strains correlated with lower surface expression of Toll-like receptor 2 (TLR2) on DCs than on monocytes. The surface expression of TLR4 on DCs was undetectable when it was analyzed by flow cytometry, but blocking this receptor decreased the TNF production in response to V. parvula, indicating that TLR4 is expressed at a low density on DCs. Gamma interferon increased the expression of TLR4 on DCs and also potentiated the cytokine response to the gram-negative strains. Our results indicate that when monocytes differentiate into DCs, their ability to respond to different commensal bacteria dramatically changes, and they become unresponsive to probiotic gram-positive bacteria. These results may have important implications for the abilities of different groups of commensal bacteria to regulate mucosal and systemic immunity.

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Section: Discussionsupporting

confidence: 61%

Pattern of Cytokine Responses to Gram-Positive and Gram-Negative Commensal Bacteria Is Profoundly Changed when Monocytes Differentiate into Dendritic Cells

Karlsson¹,

Larsson²,

Wold

et al. 2004

Infect Immun

120

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“…The IgG2 dominant response suggests that the adaptive T-cell response to the pilus-linked MBP could be predominantly T helper 1 (Th1) type. Similarly, a predominant Th1 response was also seen when other live L. lactis vaccines were administrated at mucosal surfaces (11,30). Th1 cells contribute to the humoral response by supporting the production of IgG2a, while inhibiting the formation of other IgG subclasses, such as IgG1.…”

Section: Discussionmentioning

confidence: 93%

A Foreign Protein Incorporated on the Tip of T3 Pili in Lactococcus lactis Elicits Systemic and Mucosal Immunity

et al. 2010

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The use of Lactococcus lactis to deliver a chosen antigen to the mucosal surface has been shown to elicit an immune response in mice and is a possible method of vaccination in humans. The recent discovery on Gram-positive bacteria of pili that are covalently attached to the bacterial surface and the elucidation of the residues linking the major and minor subunits of such pili suggests that the presentation of an antigen on the tip of pili external to the surface of L. lactis might constitute a successful vaccine strategy. As a proof of principle, we have fused a foreign protein (the Escherichia coli maltose-binding protein) to the C-terminal region of the native tip protein (Cpa) of the T3 pilus derived from Streptococcus pyogenes and expressed this fusion protein (MBP*) in L. lactis. We find that MBP* is incorporated into pili in this foreign host, as shown by Western blot analyses of cell wall proteins and by immunogold electron microscopy. Furthermore, since the MBP* on these pili retains its native biological activity, it appears to retain its native structure. Mucosal immunization of mice with this L. lactis strain expressing pilus-linked MBP* results in production of both a systemic and a mucosal response (IgG and IgA antibodies) against the MBP antigen. We suggest that this type of mucosal vaccine delivery system, which we term UPTOP (for unhindered presentation on tips of pili), may provide an inexpensive and stable alternative to current mechanisms of immunization for many serious human pathogens.Pili of Gram-positive bacteria are filamentous structures that extend outward from the bacterial surface and are covalently anchored to the bacterial cell wall. They are believed to be the primary means of attachment to the appropriate environmental receptor for the organism, which, for pathogens, is within the human host. The backbone of the pilus in Gram-positive bacteria is composed of multiple covalently linked identical subunits (major pilin), to which one or more minor pilin subunits are covalently attached. Pilin proteins are synthesized with an N-terminal Sec signal, which is cleaved during transit through the cytoplasmic membrane, and a C-terminal cell wall sorting signal (CWSS), which contains an LPXTG (or similar) amino acid motif, followed by a hydrophobic region and a positively charged C terminus. Pilus assembly is catalyzed by a pilus-specific sortase family transpeptidase, which cleaves the CWSS motif between the threonine (T) and glycine (G) residues and forms a covalent bond between this T and a conserved lysine (K) residue of another major pilin subunit. As this process repeats, the pilus is polymerized until it is covalently linked to the cell wall by either the "housekeeping" sortase, which is responsible for anchoring most surface proteins of Gram-positive bacteria to the cell wall, or the pilusspecific sortase (for reviews, see references 21, 35, and 38).We have been investigating assembly of T3 pili of Streptococcus pyogenes, an important human pathogen. In this organism, the T3 pilus lo...

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“…For example, L. lactis and L. plantarum induced production of IL-12 and IFN-by splenocytes when the LAB and an allergen were coadministered intranasally to mice (Repa et al, 2003). L. fermentum strain CECT5716 enhanced the Th1 responses induced by an influenza vaccine in addition to enhancing virus neutralizing antibody responses (Olivares et al, 2007).…”

Section: Dose Effects Of La On T Cell Responsesmentioning

confidence: 99%

Dose Effects of LAB on Modulation of Rotavirus Vaccine Induced Immune Responses

Yuan¹,

Wen²,

Liu³

et al. 2013

Lactic Acid Bacteria - R &Amp; D for Food, Health and Livestock Purposes

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Mucosal co-application of lactic acid bacteria and allergen induces counter-regulatory immune responses in a murine model of birch pollen allergy

Cited by 119 publications

References 47 publications

Pattern of Cytokine Responses to Gram-Positive and Gram-Negative Commensal Bacteria Is Profoundly Changed when Monocytes Differentiate into Dendritic Cells

Pattern of Cytokine Responses to Gram-Positive and Gram-Negative Commensal Bacteria Is Profoundly Changed when Monocytes Differentiate into Dendritic Cells

A Foreign Protein Incorporated on the Tip of T3 Pili in Lactococcus lactis Elicits Systemic and Mucosal Immunity

Dose Effects of LAB on Modulation of Rotavirus Vaccine Induced Immune Responses

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