<i>Bordetella pertussis</i>-Infected Human Monocyte-Derived Dendritic Cells Undergo Maturation and Induce Th1 Polarization and Interleukin-23 Expression

Fedele, Giorgio; Stefanelli, Paola; Spensieri, Fabiana; Fazio, Cecilia; Mastrantonio, Paola; Ausiello, Clara Maria

doi:10.1128/iai.73.3.1590-1597.2005

Cited by 58 publications

(75 citation statements)

References 47 publications

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“…We have previously demonstrated that incubation of human MDDC with B. pertussis induced a Th1 predominant polarization and expression of IL-23, involved in Th17 cell expansion, in the absence of the Th1-inducing cytokine IL-12p70 (21,22). Furthermore, evidence is accumulating to show that Bordetella infection might bias the host response toward a Th17 response (40,41).…”

Section: Discussionmentioning

confidence: 99%

“…To evaluate the potential of MDDC to polarize T lymphocytes, experiments were performed using allogeneic T cells purified from PBMC by negative sorting with magnetic beads (pan-T cell kit; Miltenyi Biotec) (21). MDDC (0.5 ϫ 10 5 /ml) and T cells (0.5 ϫ 10 6 /ml) were cultured in complete medium in 24-well plates (Corning).…”

Section: Polarization Of T Lymphocytesmentioning

confidence: 99%

“…Total RNA was extracted from MDDC at different time points and reverse transcription was conducted as previously described (21,22). PCR was performed, amplifying the target cDNA transcripts and the ␤-actin cDNA as endogenous control.…”

Section: Mrna Cytokine Expression By Taqman Real-time Rt-pcr Analysismentioning

confidence: 99%

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Lipopolysaccharides from Bordetella pertussis and Bordetella parapertussis Differently Modulate Human Dendritic Cell Functions Resulting in Divergent Prevalence of Th17-Polarized Responses

Fedele

Nasso

Spensieri

et al. 2008

The Journal of Immunology

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Bordetella pertussis and B. parapertussis are the etiological agents of pertussis, yet the former has a higher incidence and is the cause of a more severe disease, in part due to pertussis toxin. To identify other factors contributing to the different pathogenicity of the two species, we analyzed the capacity of structurally different lipooligosaccharide (LOS) from B. pertussis and LPS from B. parapertussis to influence immune functions regulated by dendritic cells. Either B. pertussis LOS and B. parapertussis LPS triggered TLR4 signaling and induced phenotypic maturation and IL-10, IL-12p40, IL-23, IL-6, and IL-1β production in human monocyte-derived dendritic cells (MDDC). B. parapertussis LPS was a stronger inducer of all these activities as compared with B. pertussis LOS, with the notable exception of IL-1β, which was equally produced. Only B. parapertussis LPS was able to induce IL-27 expression. In addition, although MDDC activation induced by B. parapertussis LPS was greatly dependent on soluble CD14, B. pertussis LOS activity was CD14-independent. The analysis of the intracellular pathways showed that B. parapertussis LPS and B. pertussis LOS equally induced IκBα and p38 MAPK phosphorylation, but B. pertussis LOS triggered ERK1/2 phosphorylation more rapidly and at higher levels than B. parapertussis LPS. Furthermore, B. pertussis LOS was unable to induce MyD88-independent gene induction, which was instead activated by B. parapertussis LPS, witnessed by STAT1 phosphorylation and induction of the IFN-dependent genes, IFN regulatory factor-1 and IFN-inducible protein-10. These differences resulted in a divergent regulation of Th cell responses, B. pertussis LOS MDDC driving a predominant Th17 polarization. Overall, the data observed reflect the different structure of the two LPS and the higher Th17 response induced by B. pertussis LOS may contribute to the severity of pertussis in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Polarization Of T Lymphocytesmentioning

confidence: 99%

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Lipopolysaccharides from Bordetella pertussis and Bordetella parapertussis Differently Modulate Human Dendritic Cell Functions Resulting in Divergent Prevalence of Th17-Polarized Responses

Fedele

Nasso

Spensieri

et al. 2008

The Journal of Immunology

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“…Moreover, infection of human DCs with Bordetella pertussis inhibits IL-12p35 production through cAMP induction. Such DCs produce IL-23 but no IL-12p70, but they drive Th1 responses in vitro (76,77). Thus, the production of IL-23 might also affect the induction of Th cell responses in nonhuman primates and may have influenced, in the context of other yet unidentified chemokines/cytokines and stimulatory membranebound molecules, the quality of the immune response induced by the ex vivo-activated DCs.…”

Section: Discussionmentioning

confidence: 99%

IL-12-Impaired and IL-12-Secreting Dendritic Cells Produce IL-23 upon CD154 Restimulation

Jasny

Eisenblätter

Mätz‐Rensing

et al. 2008

The Journal of Immunology

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Experimental studies in monkeys on the basis of ex vivo-generated, reinjected dendritic cells (DCs) allow investigations of primate DC biology in vivo. To study in vitro and in vivo properties of DCs with a reduced capacity to produce IL-12, we adapted findings obtained in vitro with human cells to the rhesus macaque model. Following exposure of immature monocyte-derived monkey DCs to the immunomodulating synthetic polypeptide glatiramer acetate (GA) and to dibutyryl-cAMP (d-cAMP; i.e., a cAMP enhancer that activates DCs but inhibits the induction of Th1 immune responses), the resulting DCs displayed a mature phenotype with enhanced Ag-specific T cell stimulatory function, notably also for memory Th1 cells. Phosphorylation of p38 MAPK was not induced in GA/d-cAMP-activated DCs. Accordingly, these cells secreted significantly less IL-12p40 (p ≤ 0.001) than did cytokine-activated cells. However, upon restimulation with rhesus macaque CD154, GA/d-cAMP-activated DCs produced IL-12p40/IL-23. Additionally, DCs activated by proinflammatory cytokines following protocols for the generation of cells used in clinical studies secreted significantly more IL-23 upon CD154 restimulation than following prior activation. Two days after intradermal injection, GA/d-cAMP-activated fluorescence-labeled DCs were detected in the T cell areas of draining lymph nodes. When similarly injected, GA/d-cAMP as well as cytokine-activated protein-loaded DCs induced comparable Th immune responses characterized by secretion of IFN-γ, TNF, and IL-17, and transiently expanded FOXP3+ regulatory T cells. Reactivation of primate DCs through CD154 considerably influences their immmunostimulatory properties. This may have a substantial impact on the development of innovative vaccine approaches.

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“…However, with some microbes and some purified microbial products more effective induction of IL-23 compared to IL-12 has been show to occur. This happens with Bordetella pertussis [19] as well as with stimulation by peptidoglycan from Staphylococcus aureus [20]. In addition, various toll-like receptor (TLR) ligands were shown to differentially stimulate IL-12 and IL-23 production from dendritic cells (DCs) [21,22].…”

Section: Discussionmentioning

confidence: 99%

Enhanced viral immunoinflammatory lesions in mice lacking IL-23 responses

Kim

Sarangi

Azkur

et al. 2008

Microbes and Infection

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Herpes simplex virus (HSV) infection of the cornea culminates in an immunopathological lesion (stromal keratitis -SK) that impairs vision. This report shows that HSV infection results in IL-23 up-regulation, but if this response fails to occur, as was noted in p19-/-mice, the severity of lesions, their incidence and the level of viral induced angiogenesis were significantly increased compared to wild-type (WT) animals (p < 0.05). The higher disease severity in p19-/-mice appeared to be the consequence of an increased IL-12 response that in turn led to the induction of higher numbers of IFN-γ producing CD4 + T cells, the principal orchestrators of SK. Our results indicate that the severity of HSV induced immunopathological lesions may be mainly the consequence of IL-12 driven Th1 T cell reactions rather than the action of IL-17 producing cells controlled by IL-23.

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Bordetella pertussis-Infected Human Monocyte-Derived Dendritic Cells Undergo Maturation and Induce Th1 Polarization and Interleukin-23 Expression

Cited by 58 publications

References 47 publications

Lipopolysaccharides from Bordetella pertussis and Bordetella parapertussis Differently Modulate Human Dendritic Cell Functions Resulting in Divergent Prevalence of Th17-Polarized Responses

Lipopolysaccharides from Bordetella pertussis and Bordetella parapertussis Differently Modulate Human Dendritic Cell Functions Resulting in Divergent Prevalence of Th17-Polarized Responses

IL-12-Impaired and IL-12-Secreting Dendritic Cells Produce IL-23 upon CD154 Restimulation

Enhanced viral immunoinflammatory lesions in mice lacking IL-23 responses

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