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- Lundell, Anna-Carin, 1976, et al.
(författare)
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High circulating immunoglobulin A levels in infants are associated with intestinal toxigenic Staphylococcus aureus and a lower frequency of eczema.
- 2009
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Ingår i: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 1365-2222. ; 39:5, s. 662-70
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intestinal bacteria trigger IgA production and delayed maturation of mucosal IgA response is linked to allergy development. OBJECTIVE: Our aim was to investigate if plasma levels of IgA or APRIL (a proliferation inducing ligand), an important factor for IgA class switch recombination, in infancy correlates with intestinal colonization by any specific bacteria or yeast. We also examined if plasma IgA or APRIL levels are related to sensitization and the development of eczema. METHODS: IgA was quantified in plasma obtained from infants at birth and at 4 and 18 months of age and APRIL was measured at 4 months of age. Colonization by major bacterial groups and yeast was followed in the first 8 weeks of life by quantitative culture of stool samples. A clinical evaluation regarding the presence of allergen-specific IgE or eczema and eosinophil counts in blood was performed at 18 months of age. RESULTS: In multiple linear regression analysis, only colonization by Staphylococcus aureus strains producing toxins with superantigen function (SEA-D or TSST-1) made an independent contribution to plasma IgA levels at 4 months of age. Further, increased levels of APRIL in plasma at 4 months were negatively associated with sensitization while IgA plasma levels were inversely correlated to eczema development and blood eosinophil counts at 18 months of age. CONCLUSION: Early intestinal colonization by toxigenic S. aureus strains seems to promote systemic IgA responses. Furthermore, high levels of APRIL and IgA in the circulation at 4 months of age seem to correlate negatively with allergy development.
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| 2. |
- Lundell, Anna-Carin, 1976, et al.
(författare)
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Increased levels of circulating soluble CD14 but not CD83 in infants are associated with early intestinal colonization with Staphylococcus aureus
- 2007
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Ingår i: Clin Exp Allergy. ; 37:1, s. 62-71
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Soluble forms of the monocyte marker CD14 and the mature dendritic cell marker CD83 are plasma proteins with immunoregulatory functions. The physiological stimulus for their production is unclear and their possible role in allergy development is unknown. METHODS: We measured the plasma levels of soluble CD14 (sCD14) and soluble CD83 (sCD83) in 64 Swedish children in relation to intestinal bacterial colonization pattern in a prospective birth cohort. Soluble CD14 and sCD83 levels were quantified by enzyme linked immunosorbent assay in plasma obtained at birth and at 4, 18 and 36 months of age. All major aerobic and anaerobic bacteria were quantified in faecal samples obtained regularly over the first 8 weeks of life. Clinical allergy and IgE levels were evaluated at 18 months of age. RESULTS: Soluble CD14 in plasma increased during the first 18 months of life while sCD83 peaked at 4 months of age. Children who were perinatally colonized with Staphylococcus aureus had significantly higher levels of sCD14 in plasma at 4 months of age relative to non-colonized children. The levels of sCD14 were unrelated to colonization with Escherichia coli, other enterobacteria, enterococci, clostridia, Bacteroides, bifidobacteria or lactobacilli. Further, children with food allergy by 18 months tended to have lower levels of sCD14 than healthy children. Plasma levels of sCD83 were not related to either bacterial colonization pattern or allergy development. CONCLUSIONS: Perinatal colonization with S. aureus may trigger the occurrence of sCD14 in plasma, which may influence development of the infantile immune system and risk of allergy development.
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| 3. |
- Andersson Lundell, Anna-Carin, 1976, et al.
(författare)
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Cat allergen induces proinflammatory responses by human monocyte-derived macrophages but not by dendritic cells
- 2005
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Ingår i: Allergy. ; 60:9, s. 1184-91
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The upper airway mucosa of healthy humans contains a dense network of cells with dendritic morphology of which the majority express a macrophage-like phenotype (CD14+CD64+CD68+), whereas the smaller population are immature dendritic cells (DC; CD11c+CD14-). Our aim was to study the proinflammatory response of human monocytes and in vitro-generated macrophages and DC after contact with cat allergens. METHODS: Monocyte-derived DC and monocyte-derived macrophages were exposed to cat allergen extract or Escherichia coli. Purified monocytes were stimulated with allergen extracts from cat or house dust mite (HDM) or the major allergenic protein Fel d 1 and induction of proinflammatory cytokines by monocytes was analyzed before and after blocking CD14. RESULTS: We show that cat allergen extract induced tumor necrosis factor (TNF) and interleukin (IL)-6 production by CD14-positive macrophages but not by CD14-negative DC. Moreover, monocytes produced significantly higher levels of TNF in response to cat allergens than in response to HDM allergens. We observed no differences in levels of TNF and IL-6 from either macrophages or monocytes after exposure to cat allergen when comparing healthy and cat-allergic individuals. Finally, the proinflammatory cytokine production from monocytes in response to cat allergen extract but not to HDM allergen was significantly reduced by blocking CD14. CONCLUSION: These results indicate that closely related innate immune cells from the myeloid lineage respond differentially to cat allergen extract and that the pattern-recognition receptor CD14 might be one of the mediators involved in the inflammatory responses to inhalant allergens.
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| 4. |
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| 5. |
- Lundell, Anna-Carin, 1976, et al.
(författare)
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Soluble CD14 and CD83 from human neonatal antigen-presenting cells are inducible by commensal bacteria and suppress allergen-induced human neonatal Th2 differentiation
- 2007
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Ingår i: Infect Immun. ; 75:8, s. 4097-104
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Tidskriftsartikel (refereegranskat)abstract
- CD14 is expressed on the cell surface of various antigen-presenting cells, and CD83 is a maturation marker for dendritic cells (DC). CD14 and CD83 are also present as soluble proteins, and both have immunoregulatory functions. We examined whether neonatal cord blood monocytes or DC released soluble CD14 (sCD14) or sCD83 when exposed to the commensal intestinal bacteria Clostridium perfringens, Staphylococcus aureus, Lactobacillus rhamnosus, Escherichia coli, and Bacteroides fragilis. We found that the gram-positive bacteria C. perfringens and S. aureus, but not gram-negative bacteria, induced the release of sCD14 from monocytes. DC, on the other hand, released sCD14 in response to both gram-positive and gram-negative bacteria. Moreover, the expression of the virulence factor staphylococcal protein A seemed to be important for S. aureus-induced sCD14 production from both monocytes and DC. Soluble CD83 was released from DC, but not from monocytes, when exposed to both gram-positive and gram-negative bacteria. Finally, to investigate whether sCD14 or sCD83 could modulate neonatal allergen-induced T-cell differentiation, DC were exposed to birch allergen alone or in the presence of sCD14 or sCD83 and then cocultured with autologous T cells. We demonstrate that sCD14 and sCD83 inhibited the birch allergen-induced Th2 differentiation by suppressing interleukin 13 production. Together, these results suggest that the commensal intestinal flora may be an important stimulus for the developing immune system by inducing the immunoregulatory proteins sCD14 and sCD83, which may be involved in preventing T-cell sensitization to allergens in infants.
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| 6. |
- Lundell, Anna-Carin, 1976
(författare)
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Regulation of human immune responses to allergens
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The incidence of allergic diseases is increasing in the industrialized countries. Epidemiological studies indicate that there is an association between exposure to high levels of endotoxin or cat allergen during infancy and reduced risk of developing allergic diseases later in childhood. The aim of this study was to investigate if allergen extracts from birch, cat and house dust mite induce proinflammatory cytokine production from human innate immune cells. We also examined the levels of soluble CD14 (sCD14) and soluble CD83 (sCD83) in plasma during infancy and whether the early gastrointestinal bacterial colonization pattern could be related to the plasma levels of these two proteins. Finally, we investigated if bacterial components or the immunoregulatory proteins sCD14 and sCD83, would be able to modulate neonatal adaptive immune responses to birch allergen extract. To enable these studies, we optimized an in vitro model for allergic T cell sensitization using human autologous neonatal immune cells. We found that cat allergen extract induced TNF and IL-6 production from human CD14-positive monocytes and macrophages but not from CD14-negative DCs. The cytokine production from monocytes in response to cat allergen extract was reduced by blocking CD14. Both sCD14 and sCD83 were found to be present in the circulation during infancy. The plasma levels of sCD14 increased during the first 18 months of life, whereas the levels of sCD83 in plasma peaked at 4 months of age. Both proteins were found in higher amounts in plasma during infancy relative to plasma from adult individuals. We observed that children who were colonized with S. aureus at an early age had significantly higher levels of sCD14 in plasma at 4 months of age relative to children who were not colonized with this bacterium. Moreover, both neonatal monocytes and monocyte-derived dendritic cells (DCs) released sCD14 in response to S. aureus stimulation in vitro. Children with food allergy tended to have lower levels of sCD14 in plasma and were significantly less colonized with S. aureus relative to healthy children. In contrast, sCD83 was not found to be related to the intestinal bacterial colonization in vivo. However, DCs, but not monocytes, released sCD83 in response to bacterial stimulation in vitro. Birch allergen extract induced high levels of the Th2 cytokine IL-13 from neonatal T cells. Interestingly, in contrast to the Toll-like receptor 2 agonist Pam3Cys, the Toll-like receptor 4 agonist lipopolysaccharide as well as sCD14 or sCD83 were able to suppress birch allergen-induced Th2 differentiation. In conclusion, our results suggest that strong activation of the developing immune system might be involved in down-regulating immune responses that may lead to allergic diseases in children. This effect may be mediated either directly via stimulation of antigen-presenting cells, or indirectly via induction of soluble immunoregulatory proteins such as sCD14 and sCD83.
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