Differential Responses of Human Dendritic Cells to Live or Inactivated Staphylococcus aureus: Impact on Cytokine Production and T Helper Expansion

A potential concern with bacteriophage (phage) therapeutics is a host-versus-phage response in which the immune system may neutralize or destroy phage particles and thus impair therapeutic efficacy, or a strong inflammatory response to repeated phage exposure might endanger the patient. Current literature is discrepant with regard to the nature and magnitude of innate and adaptive immune response to phages. The purpose of this work was to study the potential effects of Staphylococcus aureus phage K on the activation of human monocyte-derived dendritic cells. Since phage K acquired from ATCC was isolated around 90 years ago, we first tested its activity against a panel of 36 diverse S. aureus clinical isolates from military patients and found that it was lytic against 30/36 (83%) of strains. Human monocyte-derived dendritic cells were used to test for an in vitro phage-specific inflammatory response. Repeated experiments demonstrated that phage K had little impact on the expression of pro- and anti-inflammatory cytokines, or on MHC-I/II and CD80/CD86 protein expression. Given that dendritic cells are potent antigen-presenting cells and messengers between the innate and the adaptive immune systems, our results suggest that phage K does not independently affect cellular immunity or has a very limited impact on it.

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Pregnancy associated hormones modulate the cytokine production but not the phenotype of PBMC-derived human dendritic cells

European Journal of Obstetrics & Gynecology and Reproductive Biology ◽

10.1016/j.ejogrb.2005.02.017 ◽

2005 ◽

Vol 122 (1) ◽

pp. 85-94 ◽

Cited By ~ 39

Author(s):

Barbara Huck ◽

Thomas Steck ◽

Marion Habersack ◽

Johannes Dietl ◽

Ulrike Kämmerer

Keyword(s):

Dendritic Cells ◽

Cytokine Production ◽

Human Dendritic Cells

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CD47 Engagement Inhibits Cytokine Production and Maturation of Human Dendritic Cells

The Journal of Immunology ◽

10.4049/jimmunol.164.4.2193 ◽

2000 ◽

Vol 164 (4) ◽

pp. 2193-2199 ◽

Cited By ~ 101

Author(s):

C. E. Demeure ◽

H. Tanaka ◽

V. Mateo ◽

M. Rubio ◽

G. Delespesse ◽

...

Keyword(s):

Dendritic Cells ◽

Cytokine Production ◽

Human Dendritic Cells

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Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma

Blood ◽

10.1182/blood-2008-03-143222 ◽

2008 ◽

Vol 112 (7) ◽

pp. 2878-2885 ◽

Cited By ~ 127

Author(s):

Kavita M. Dhodapkar ◽

Scott Barbuto ◽

Phillip Matthews ◽

Anjli Kukreja ◽

Amitabha Mazumder ◽

...

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Th17 Cells ◽

T Helper ◽

Tumor Bed ◽

Distinct Lineage ◽

Human Dendritic Cells ◽

Antigen Presenting ◽

Dc Maturation

Abstract IL17-producing (Th17) cells are a distinct lineage of T helper cells that regulate immunity and inflammation. The role of antigen-presenting cells in the induction of Th17 cells in humans remains to be fully defined. Here, we show that human dendritic cells (DCs) are efficient inducers of Th17 cells in culture, including antigen-specific Th17 cells. Although most freshly isolated circulating human Th17 cells secrete IL17 alone or with IL2, those induced by DCs are polyfunctional and coexpress IL17 and IFNγ (Th17-1 cells). The capacity of DCs to expand Th17-1 cells is enhanced upon DC maturation, and mature DCs are superior to monocytes for the expansion of autologous Th17 cells. In myeloma, where tumors are infiltrated by DCs, Th17 cells are enriched in the bone marrow relative to circulation. Bone marrow from patients with myeloma contains a higher proportion of Th17-1 cells compared with the marrow in preneoplastic gammopathy (monoclonal gammopathy of undetermined significance [MGUS]). Uptake of apoptotic but not necrotic myeloma tumor cells by DCs leads to enhanced induction of Th17-1 cells. These data demonstrate the capacity of DCs to induce expansion of polyfunctional IL17-producing T cells in humans, and suggest a role for DCs in the enrichment of Th17-1 cells in the tumor bed.

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Staphylococcus aureusImpairs the Function of and Kills Human Dendritic Cells via the LukAB Toxin

mBio ◽

10.1128/mbio.01918-18 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 12

Author(s):

Evelien T. M. Berends ◽

Xuhui Zheng ◽

Erin E. Zwack ◽

Mickaël M. Ménager ◽

Michael Cammer ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Dendritic Cells ◽

Adaptive Immunity ◽

T Cell Activation ◽

Antigen Presenting Cells ◽

Infection Model ◽

High Morbidity ◽

Content Type ◽

Human Dendritic Cells ◽

Antigen Presenting

ABSTRACTStaphylococcus aureusis a human pathogen responsible for high morbidity and mortality worldwide. Recurrent infections with this bacterium are common, suggesting thatS. aureusthwarts the development of sterilizing immunity.S. aureusstrains that cause disease in humans produce up to five different bicomponent toxins (leukocidins) that target and lyse neutrophils, innate immune cells that represent the first line of defense againstS. aureusinfections. However, little is known about the role of leukocidins in blunting adaptive immunity. Here, we explored the effects of leukocidins on human dendritic cells (DCs), antigen-presenting cells required for the development of adaptive immunity. Using anex vivoinfection model of primary human monocyte-derived dendritic cells, we found thatS. aureus, including strains from different clonal complexes and drug resistance profiles, effectively kills DCs despite efficient phagocytosis. Although all purified leukocidins could kill DCs, infections with live bacteria revealed thatS. aureustargets and kills DCs primarily via the activity of leukocidin LukAB. Moreover, using coculture experiments performed with DCs and autologous CD4+T lymphocytes, we found that LukAB inhibits DC-mediated activation and proliferation of primary human T cells. Taken together, the data determined in the study reveal a novel immunosuppressive strategy ofS. aureuswhereby the bacterium blunts the development of adaptive immunity via LukAB-mediated injury of DCs.IMPORTANCEAntigen-presenting cells such as dendritic cells (DCs) fulfill an indispensable role in the development of adaptive immunity by producing proinflammatory cytokines and presenting microbial antigens to lymphocytes to trigger a faster, specific, and long-lasting immune response. Here, we studied the effect ofStaphylococcus aureustoxins on human DCs. We discovered that the leukocidin LukAB hinders the development of adaptive immunity by targeting human DCs. The ability ofS. aureusto blunt the function of DCs could help explain the high frequency of recurrentS. aureusinfections. Taken together, the results from this study suggest that therapeutically targeting theS. aureusleukocidins may boost effective innate and adaptive immune responses by protecting innate leukocytes, enabling proper antigen presentation and T cell activation.

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Immunopotent Polysaccharides of Different Sources Selectively Activate Human Dendritic Cells.

Blood ◽

10.1182/blood.v106.11.3873.3873 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3873-3873

Author(s):

Godfrey ChiFung Chan ◽

W.K. Chan ◽

H.K. Law ◽

Z.B. Lin ◽

Y.L. Lau

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

T Helper ◽

T Helper 1 ◽

Xtt Assay ◽

Peripheral Blood Mononuclear ◽

Human Dendritic Cells

Abstract Background: Purified polysaccharides extracted from plants and fungi have been shown to induce immune responses in-vivo and vitro over the past decade. Currently, most of these polysaccharides are found to be glucan but with different branch structure and sizes. Their relative potency and effect on human immune cells remains unknown. This study aims to compare their relative effect on human dendritic cell, the most potent antigen presenting cell. Materials & Methods: We selected 2 prototypes of purified polysaccharides extracted from: 1) Ganoderma lucidum (GL, Lingzhi, Reishi) mycelium, a widely used herb with long and branching β (1® 3), (1® 6) glucan structure (provided by Prof. Lin ZB, Beijing) and 2) Barley with shorter and different branching β (1® 3), (1® 4) structure (provided by Prof. Cheung VNK, NY). Their characteristics and chemical properties had been reported previously. Human peripheral blood mononuclear cells (PBMCs) proliferation was studied by XTT assay. Human dendritic cells (DCs) were derived from monocytes and maturation of DCs were determined by: a) immunophenotypic shift using flow cytometer; 2) dextran endocytosis assay and 3) mixed lymphocytes reaction. Cytokine secretions were determined by ELISA test. Comparisons between means were by nonparametric Student’s t test (2-tailed). Results: We found that purified polysaccharides from GL but not barley could induce PBMCs proliferation and maturation of DCs. GL polysaccharides could enhance phenotypic and functional maturation of DCs with significant IL-12 and IL-10 production. DCs were relatively inert to Barley glucans stimulation. However, both polysaccharides did not polarize T cells into the direction of T helper 1, T helper 2 or regulatory T cells. Conclusions: Our study shown that purified polysaccharides extracted from plants and fungi have different effect on human DCs and their potency and effects are probably affected by their respective sources and structures.

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