Immune response of human monocyte-derived dendritic cells to co-infection of influenza virus and Streptococcus pneumoniae

ABSTRACTA functional immune response is crucial to prevent and limit infections withStreptococcus pneumoniae. Dendritic cells (DCs) play a central role in orchestrating the adaptive and innate immune responses by communicating with other cell types via antigen presentation and secretion of cytokines. In this study, we set out to understand how pneumococci activate human monocyte-derived DCs to produce interleukin-12 (IL-12) p70, an important cytokine during pneumococcal infections. We show that IL-12p70 production requires uptake of bacteria as well as the presence of the adaptor molecule TRIF, which is known to transfer signals of Toll-like receptor 3 (TLR3) or TLR4 from the endosome into the cell. While TLR4 is redundant for IL-12p70 production in DCs, we found that TLR3 is required to induce full IL-12p70 secretion. Influenza A virus (IAV) infection of DCs did not induce IL-12p70 but markedly upregulated TLR3 expression that during coinfection withS. pneumoniaesignificantly enhanced IL-12p70 secretion. Finally, we show that pneumococcal RNA can act as a bacterial stimulus for TLR3 and that it is a key signal to induce IL-12p70 production during challenge of DCs with pneumococci.IMPORTANCEStreptococcus pneumoniae, a common colonizer of the nose, is the causative agent of severe and deadly diseases. A well-orchestrated immune response is vital to prevent and limit these diseases. Dendritic cells (DCs) reside in the mucosal linings of the lungs and sample antigens. They are activated by pathogens to present antigens and secrete cytokines. While many studies focus on murine models, we focused our work on human monocyte-derived DCs. We found that pneumococcal RNA is an important stimulus in DCs to activate the endosomal receptor TLR3, a receptor previously not identified to sense pneumococci, and its adaptor molecule TRIF. This leads to secretion of the cytokine interleukin-12 (IL-12). Severe pneumococcal pneumonia occurs closely after influenza A virus (IAV) infection. We show that IAV infection upregulates TLR3 in DCs, which sensitizes the cells to endosomal pneumococcal RNA. This new insight contributes to unlock the interplay between pneumococci, IAV, and humans.

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Polarization of Allogeneic T-Cell Responses by Influenza Virus-Infected Dendritic Cells

Journal of Virology ◽

10.1128/jvi.74.17.7738-7744.2000 ◽

2000 ◽

Vol 74 (17) ◽

pp. 7738-7744 ◽

Cited By ~ 25

Author(s):

Sangkon Oh ◽

Maryna C. Eichelberger

Keyword(s):

Immune Response ◽

T Cells ◽

Dendritic Cells ◽

Influenza Virus ◽

T Cell ◽

Interleukin 2 ◽

Dependent Manner ◽

Ifn Γ ◽

High Doses ◽

Type Response

ABSTRACT The developing immune response in the lymph nodes of mice infected with influenza virus has both Th1- and Th2-type characteristics. Modulation of the interactions between antigen-presenting cells and T cells is one mechanism that may alter the quality of the immune response. We have previously shown that the ability of dendritic cells (DC) to stimulate the proliferation of alloreactive T cells is changed by influenza virus due to viral neuraminidase (NA) activity. Here we show that DC infected with influenza virus A/PR/8/34 (PR8) stimulate T cells to produce different types of cytokines in a dose-dependent manner. Optimal amounts of the Th1-type cytokines interleukin-2 (IL-2) and gamma interferon (IFN-γ) were produced from T cells stimulated by DC infected with low doses of PR8, while the Th2-type cytokines IL-4 and IL-10 were produced only in response to DC infected with high doses of PR8. IL-2 and IFN-γ levels corresponded with T-cell proliferation and were dependent on the activity of viral NA on the DC surface. In contrast, IL-4 secretion required the treatment of T cells with NA. Since viral particles were released only from DC that are infected with high doses of PR8, our results suggest that viral NA on newly formed virus particles desialylates T-cell surface molecules to facilitate a Th2-type response. These results suggest that the activity of NA may contribute to the mixed Th-type response observed during influenza virus infection.

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Azithromycin modulates immune response of human monocyte-derived dendritic cells and CD4 + T cells

International Immunopharmacology ◽

10.1016/j.intimp.2016.09.012 ◽

2016 ◽

Vol 40 ◽

pp. 318-326 ◽

Cited By ~ 16

Author(s):

Syh-Jae Lin ◽

Ming-Ling Kuo ◽

Hsiu-Shan Hsiao ◽

Pei-Tzu Lee

Keyword(s):

Immune Response ◽

T Cells ◽

Dendritic Cells ◽

Cd4 T Cells ◽

Human Monocyte

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Vibrio parahaemolyticus Flagellin Stimulates the Maturation of Human Monocyte-Derived Dendritic Cells and Elicits Th1-Type Immune Response.

Blood ◽

10.1182/blood.v106.11.3872.3872 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3872-3872

Author(s):

Hyun-Kyu Kang ◽

Myong-Suk Park ◽

Shee-Eun Lee ◽

Joon-Haeng Rhee ◽

Jung-Sun Park ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Vibrio Parahaemolyticus ◽

Human Monocyte ◽

Phenotypic Change ◽

Target Cells ◽

Maximal Effect ◽

Dependent Manner ◽

Functional Maturation

Abstract Flagellin, the principal component of bacterial flagella, interacts with Toll-like receptor (TLR5) and induces the generation of a pro-inflammation response and activation of host dendritic cells (DCs) in vivo. In this study, we investigated the role of Vibrio parahaemolyticus (V. parahaemolyticus)-derived flagellin as a DC maturation-inducing molecule. V. parahemolyticus-derived flagellin (100–1,000 ng/ml) induced the maturation of human monocyte-derived dendritic cells in a concentration-dependent manner with maximal effect at 500 ng/ml of flagellin as determined by increased levels of surface markers, namely, CD1a, CD80, CD86, CD83, and HLA-DR, a response which could be compared with the phenotypic change in immature DCs (iDCs) treated with lipopolysaccharide (LPS) or cytokine cocktails (CC) with TNF-α, IL-1β, IL-6, and PGE2. Moreover, V. parahaemolyticus-derived flagellin also reduced phagocytic activity, and increased IL-12 production in a polymyxin B-insensitive manner and DC-mediated T cell proliferation, which is comparable with that of LPS- or CC-treated iDCs at several responder to stimulator ratios, suggesting the functional maturation of DCs by V. parahaemolyticus-derived flagellin. Maturation of DCs by V. parahaemolyticus-derived flagellin also elicited a significant increase in specific cytotoxic activity against target cells at several effector to target cells ratios as determined by 51Cr-release assay, and induced Th1-type immune response, such as increase in INF-γ producing cells, determined by ELISPOT assay and analysis of intracellular cytokine staining assay. Taken together, this study demonstrates the role of V. parahaemolyticus-derived flagellin in the functional maturation of DCs, and suggests that V. parahaemolyticus-derived flagellin as a useful molecule for the development of a DC-based immunotherapy against tumors.

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Human monocyte-derived dendritic cells differentiated in the presence of IL-2 produce proinflammatory cytokines and prime Th1 immune response

Journal of Leukocyte Biology ◽

10.1189/jlb.1105690 ◽

2006 ◽

Vol 80 (3) ◽

pp. 555-562 ◽

Cited By ~ 29

Author(s):

N. Sanarico

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Proinflammatory Cytokines ◽

Human Monocyte ◽

Th1 Immune Response

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The study of immune response to co-infection of influenza virus and Streptococcus pneumoniae

10.5353/th_b5106508 ◽

2013 ◽

Author(s):

Yuet Wu

Keyword(s):

Immune Response ◽

Influenza Virus ◽

Streptococcus Pneumoniae

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Glycans from avian influenza virus are recognized by chicken dendritic cells and are targets for the humoral immune response in chicken

Molecular Immunology ◽

10.1016/j.molimm.2013.06.007 ◽

2013 ◽

Vol 56 (4) ◽

pp. 452-462 ◽

Cited By ~ 8

Author(s):

Eveline D. de Geus ◽

Boris Tefsen ◽

Daphne A. van Haarlem ◽

Willem van Eden ◽

Irma van Die ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Influenza Virus ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Humoral Immune Response ◽

Humoral Immune

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Bordetella pertussis Naturally Occurring Isolates with Altered Lipooligosaccharide Structure Fail To Fully Mature Human Dendritic Cells

Infection and Immunity ◽

10.1128/iai.02197-14 ◽

2014 ◽

Vol 83 (1) ◽

pp. 227-238 ◽

Cited By ~ 8

Author(s):

Jolanda Brummelman ◽

Rosanne E. Veerman ◽

Hendrik Jan Hamstra ◽

Anna J. M. Deuss ◽

Tim J. Schuijt ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Bordetella Pertussis ◽

Lipid A ◽

Whooping Cough ◽

Human Monocyte ◽

Innate Immune ◽

Clinical Isolates ◽

Immune Recognition ◽

Content Type

Bordetella pertussisis a Gram-negative bacterium and the causative agent of whooping cough. Despite high vaccination coverage, outbreaks are being increasingly reported worldwide. Possible explanations include adaptation of this pathogen, which may interfere with recognition by the innate immune system. Here, we describe innate immune recognition and responses to differentB. pertussisclinical isolates. By using HEK-Blue cells transfected with different pattern recognition receptors, we found that 3 out of 19 clinical isolates failed to activate Toll-like receptor 4 (TLR4). These findings were confirmed by using the monocytic MM6 cell line. Although incubation with high concentrations of these 3 strains resulted in significant activation of the MM6 cells, it was found to occur mainly through interaction with TLR2 and not through TLR4. When using live bacteria, these 3 strains also failed to activate TLR4 on HEK-Blue cells, and activation of MM6 cells or human monocyte-derived dendritic cells was significantly lower than activation induced by the other 16 strains. Mass spectrum analysis of the lipid A moieties from these 3 strains indicated an altered structure of this molecule. Gene sequence analysis revealed mutations in genes involved in lipid A synthesis. Findings from this study indicate thatB. pertussisisolates that do not activate TLR4 occur naturally and that this phenotype may give this bacterium an advantage in tempering the innate immune response and establishing infection. Knowledge on the strategies used by this pathogen in evading the host immune response is essential for the improvement of current vaccines or for the development of new ones.

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Different Transcriptional Profiles of Human Monocyte-Derived Dendritic Cells Infected with Distinct Strains ofMycobacterium tuberculosisandMycobacterium bovisBacillus Calmette-Guérin

Clinical and Developmental Immunology ◽

10.1155/2011/741051 ◽

2011 ◽

Vol 2011 ◽

pp. 1-14 ◽

Cited By ~ 10

Author(s):

Nunzia Sanarico ◽

Alessia Colone ◽

Manuela Grassi ◽

Viviana Speranza ◽

Daniela Giovannini ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Dendritic Cells ◽

Mycobacterium Tuberculosis ◽

Expression Profiles ◽

Laboratory Strain ◽

Human Monocyte ◽

Bacillus Calmette Guerin ◽

Intracellular Growth ◽

Strain Dependent

In order to analyze dendritic cells (DCs) activation following infection with different mycobacterial strains, we studied the expression profiles of 165 genes of human monocyte-derived DCs infected with H37Rv, a virulentMycobacterium tuberculosis(MTB) laboratory strain, CMT97, a clinical MTB isolate,Mycobacterium bovisbacillus Calmette-Guérin (BCG), Aventis Pasteur, and BCG Japan, both employed as vaccine against tuberculosis. The analysis of the gene expression reveals that, despite a set of genes similarly modulated, DCs response resulted strain dependent. In particular, H37Rv significantly upregulated EBI3 expression compared with BCG Japan, while it was the only strain that failed to release a significant IL-10 amount. Of note, BCG Japan showed a marked increase in CCR7 and TNF-αexpression regarding both MTB strains and it resulted the only strain failing in exponential intracellular growth. Our results suggest that DCs display the ability to elicit a tailored strain-specific immune response.

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