scholarly journals Human Dendritic Cells following Aspergillus fumigatus Infection Express the CCR7 Receptor and a Differential Pattern of Interleukin-12 (IL-12), IL-23, and IL-27 Cytokines, Which Lead to a Th1 Response

2006 ◽  
Vol 74 (3) ◽  
pp. 1480-1489 ◽  
Author(s):  
Valérie Gafa ◽  
Roberto Lande ◽  
Maria Cristina Gagliardi ◽  
Martina Severa ◽  
Elena Giacomini ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Aspergillus Fumigatus ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Th1 Response ◽  
Ifn Γ ◽  
Human Dendritic Cells ◽  
The Impact

ABSTRACT Aspergillus fumigatus is the most prevalent airborne fungal pathogen and causes fatal invasive aspergillosis in immunocompromised patients. Given the essential role of dendritic cells (DC) in initiating and regulating immune responses, we investigated the impact of A. fumigatus conidial infection on human DC. A. fumigatus conidia were rapidly internalized and induced the release of tumor necrosis factor alpha within the first 8 h. After A. fumigatus infection, the majority of DC underwent full maturation, although CCR7 expression was observed only in DC that had internalized the conidia. Additionally, the analysis of regulatory cytokines showed that infected DC simultaneously produced interleukin-12p70 (IL-12p70) and significant amounts of IL-10. IL-10 neutralization was not able to further increase IL-12p70 production from infected DC. Whereas the central role of IL-12 in the generation of Th1 cells has long been appreciated, recently two other members of the IL-12 family, IL-23 and IL-27, were reported to play important roles in the regulation of gamma interferon (IFN-γ) production from naïve and memory T cells. A. fumigatus-infected DC were also able to express high levels of IL-23p19 and low levels of IL-27p28 at later stages of infection. According to this expression pattern, A. fumigatus-infected DC were able to prime IFN-γ production of naïve T cells. Thus, this study on the expression of the new IL-12 family members controlling the Th1 response sheds light on a novel aspect of the contribution of DC to anti-Aspergillus immunity.

scholarly journals Infection of Human Dendritic Cells with a Mycobacterium tuberculosis sigE Mutant Stimulates Production of High Levels of Interleukin-10 but Low Levels of CXCL10: Impact on the T-Cell Response

2006 ◽  
Vol 74 (6) ◽  
pp. 3296-3304 ◽  
Author(s):  
Elena Giacomini ◽  
Ambar Sotolongo ◽  
Elisabetta Iona ◽  
Martina Severa ◽  
Maria Elena Remoli ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Mycobacterium Tuberculosis ◽  
Human Monocyte ◽  
Interleukin 10 ◽  
T Cell Response ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Effector Cells ◽  
Human Dendritic Cells

ABSTRACT The Mycobacterium tuberculosis genome encodes 13 sigma factors. We have previously shown that mutations in some of these transcriptional activators render M. tuberculosis sensitive to various environmental stresses and can attenuate the virulence phenotype. In this work, we focused on extracytoplasmic factor σE and studied the effects induced by the deletion of its structural gene (sigE) in the infection of human monocyte-derived dendritic cells (MDDC). We found that the wild-type M. tuberculosis strain (H37Rv), the sigE mutant (ST28), and the complemented strain (ST29) were able to infect dendritic cells (DC) to similar extents, although at 4 days postinfection a reduced ability to grow inside MDDC was observed for the sigE mutant ST28. After mycobacterium capture, the majority of MDDC underwent full maturation and expressed both inflammatory cytokines, such as tumor necrosis factor alpha, and the regulatory cytokines interleukin-12 (IL-12), IL-18, and beta interferon (IFN-β). Conversely, a higher level of production of IL-10 was observed in ST28-infected MDDC compared to H37Rv- or ST29-infected cell results. However, in spite of the presence of IL-10, supernatants from ST28-infected DC induced IFN-γ production by T cells similarly to those from H37Rv-infected DC culture. On the other hand, IL-10 impaired CXCL10 production in sigE mutant-infected DC and, indeed, its neutralization restored CXCL10 secretion. In line with these results, supernatants from ST28-infected cells showed a decreased capability to recruit CXCR3+ CD4+ T cells compared to those obtained from H37Rv-infected DC culture. Thus, our findings suggest that the sigE mutant-induced secretion of IL-10 inhibits CXCL10 expression and, in turn, the recruitment of activated-effector cells involved in the formation of granulomas.

scholarly journals Protection against Intestinal Amebiasis by a Recombinant Vaccine Is Transferable by T Cells and Mediated by Gamma Interferon

2009 ◽  
Vol 77 (9) ◽  
pp. 3909-3918 ◽  
Author(s):  
Xiaoti Guo ◽  
Lisa Barroso ◽  
Steven M. Becker ◽  
David M. Lyerly ◽  
Thomas S. Vedvick ◽  
...  
Keyword(s):  
T Cells ◽  
Gamma Interferon ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Vaccine Protection ◽  
Adjuvant System ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Intestinal Amebiasis

ABSTRACT We have previously shown that vaccination with purified Entamoeba histolytica Gal/GalNAc lectin or recombinant subunits can protect mice from intestinal amebiasis upon intracecal challenge. In this study, we demonstrated with adoptive-transfer experiments that this lectin vaccine protection is mediated by T cells but not serum. The cell-mediated immune (CMI) response was characterized by significant gamma interferon (IFN-γ), interleukin 12 (IL-12), IL-2, IL-10, and IL-17 production. To move toward a human vaccine, we switched to a recombinant protein and tested a range of adjuvants and routes appropriate for humans. We found that subcutaneous delivery of LecA with IDRI's adjuvant system EM014 elicited a potent Th1-type CMI profile and provided significant protection, as measured by culture negativity (79% efficacy); intranasal immunization with cholera toxin provided 56% efficacy; and alum induced a Th2-type response that protected 62 to 68% of mice. Several antibody and CMI cytokine responses were examined for correlates of protection, and prechallenge IFN-γ+ or IFN-γ-, IL-2-, and tumor necrosis factor alpha-triple-positive CD4 cells in blood were statistically associated with protection. To test the role of IFN-γ in LecA-mediated protection, we neutralized IFN-γ in LecA-immunized mice and found that it abrogated the protection conferred by vaccination. These data demonstrate that CMI is sufficient for vaccine protection from intestinal amebiasis and reveal an important role for IFN-γ, even in the setting of alum.

scholarly journals Mannoproteins from Cryptococcus neoformans Promote Dendritic Cell Maturation and Activation

2005 ◽  
Vol 73 (2) ◽  
pp. 820-827 ◽  
Author(s):  
Donatella Pietrella ◽  
Cristina Corbucci ◽  
Stefano Perito ◽  
Giovanni Bistoni ◽  
Anna Vecchiarelli
Keyword(s):  
Cryptococcus Neoformans ◽  
Nuclear Factor Κb ◽  
Dendritic Cell Maturation ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Histocompatibility Complex ◽  
Factor Alpha ◽  
Human Dendritic Cells ◽  
Mannose Receptors

ABSTRACT Our previous data show that mannoproteins (MPs) from Cryptococcus neoformans are able to induce protective responses against both C. neoformans and Candida albicans. Here we provide evidence that MPs foster maturation and activation of human dendritic cells (DCs). Maturation was evaluated by the ability of MPs to facilitate expression of costimulatory molecules such as CD40, CD86, CD83, and major histocompatibility complex classes I and II and to inhibit receptors such as CD14, CD16, and CD32. Activation of DCs was measured by the capacity of MPs to promote interleukin-12 and tumor necrosis factor alpha secretion. DC-induced maturation and interleukin-12 induction are largely mediated by engagement of mannose receptors and presume MP internalization and degradation. DC activation leads to IκBα phosphorylation, which is necessary for nuclear factor κB transmigration into the nucleus. MP-loaded DCs are efficient stimulators of T cells and show a remarkable capacity to promote CD4 and CD8 proliferation. In conclusion, we have evidenced a novel regulatory role of MPs that promotes their candidacy as a vaccine against fungi.

scholarly journals Batf3-Dependent Dendritic Cells Promote Optimal CD8 T Cell Responses against Respiratory Poxvirus Infection

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Pritesh Desai ◽  
Vikas Tahiliani ◽  
Georges Abboud ◽  
Jessica Stanfield ◽  
Shahram Salek-Ardakani
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Vaccinia Virus ◽  
Respiratory Infection ◽  
Host Resistance ◽  
T Cell Responses ◽  
Cell Responses ◽  
Ifn Γ ◽  
The Impact

ABSTRACTRespiratory infection with vaccinia virus (VacV) elicits robust CD8+T cell responses that play an important role in host resistance. In the lung, VacV encounters multiple tissue-resident antigen-presenting cell (APC) populations, but which cell plays a dominant role in priming of virus-specific CD8+effector T cell responses remains poorly defined. We used Batf3−/−mice to investigate the impact of CD103+and CD8α+dendritic cell (DC) deficiency on anti-VacV CD8+T cell responses. We found that Batf3−/−mice were more susceptible to VacV infection, exhibiting profound weight loss, which correlated with impaired accumulation of gamma interferon (IFN-γ)-producing CD8+T cells in the lungs. This was largely due to defective priming since early in the response, antigen-specific CD8+T cells in the draining lymph nodes of Batf3−/−mice expressed significantly reduced levels of Ki67, CD25, and T-bet. These results underscore a specific role for Batf3-dependent DCs in regulating priming and expansion of effector CD8+T cells necessary for host resistance against acute respiratory VacV infection.IMPORTANCEDuring respiratory infection with vaccinia virus (VacV), a member ofPoxviridaefamily, CD8+T cells play important role in resolving the primary infection. Effector CD8+T cells clear the virus by accumulating in the infected lungs in large numbers and secreting molecules such as IFN-γ that kill virally infected cells. However, precise cell types that regulate the generation of effector CD8+T cells in the lungs are not well defined. Dendritic cells (DCs) are a heterogeneous population of immune cells that are recognized as key initiators and regulators of T-cell-mediated immunity. In this study, we reveal that a specific subset of DCs that are dependent on the transcription factor Batf3 for their development regulate the magnitude of CD8+T cell effector responses in the lungs, thereby providing protection during pulmonary VacV infection.

scholarly journals Human Dendritic Cells Stimulated via TLR7 and/or TLR8 Induce the Sequential Production of Il-10, IFN-γ, and IL-17A by Naive CD4+ T Cells

2009 ◽  
Vol 182 (6) ◽  
pp. 3372-3379 ◽  
Author(s):  
Vincent Lombardi ◽  
Laurence Van Overtvelt ◽  
Stéphane Horiot ◽  
Philippe Moingeon
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Ifn Γ ◽  
Human Dendritic Cells

Morin Promotes the Production of Th2 Cytokine by Modulating Bone Marrow-Derived Dendritic Cells

2006 ◽  
Vol 34 (04) ◽  
pp. 667-684 ◽  
Author(s):  
Chia-Yang Li ◽  
Jau-Ling Suen ◽  
Bor-Luen Chiang ◽  
Pei-Dawn Lee Chao ◽  
Shih-Hua Fang
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Dendritic Cells ◽  
Interleukin 12 ◽  
Th2 Response ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Th Differentiation ◽  
Th1 And Th2 Responses

Our previous studies had reported that morin decreased the interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-α) production in lipopolysaccharide (LPS)-activated macrophages, suggesting that morin may promote helper T type 2 (Th2) response in vivo. Dendritic cells (DCs) are the most potent antigen presenting cells and known to play a major role in the differentiation of helper T type 1 (Th1) and Th2 responses. This study aimed to reveal whether morin is able to control the Th differentiation through modulating the maturation and functions of DCs. Bone marrow-derived dendritic cells (BM-DCs) were incubated with various concentrations of morin and their characteristics were studied. The results indicated that morin significantly affects the phenotype and cytokine expression of BM-DCs. Morin reduced the production of IL-12 and TNF-α in BM-DCs, in response to LPS stimulation. In addition, the proliferative response of stimulated alloreactive T cells was significantly decreased by morin in BM-DCs. Furthermore, allogeneic T cells secreted higher IL-4 and lower IFN-γ in response to morin in BM-DCs. In conclusion, these results suggested that morin favors Th2 cell differentiation through modulating the maturation and function of BM-DCs.

scholarly journals Glyceraldehyde-3-phosphate dehydrogenase from Eimeria acervulina modulates the functions of chicken dendritic cells to boost Th1 type immune response and stimulates autologous CD4+ T cells differentiation in-vitro

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Shakeel Ahmed Lakho ◽  
Muhammad Haseeb ◽  
Jianmei Huang ◽  
Zhang Yang ◽  
Muhammad Waqqas Hasan ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immunoblot Analysis ◽  
Eimeria Acervulina ◽  
Ifn Γ ◽  
Negative Controls ◽  
Th1 Polarization ◽  
Dc Maturation

AbstractDendritic cells (DCs) play a pivotal role to amplify antigen-specific immune responses. Antigens that sensitize T cells via antigen-presentation by DCs could enhance the capacity of host immunity to fight infections. In this study, we tested the immunogenic profiles of chicken DCs towards Glyceraldehyde-3-phosphate dehydrogenase from Eimeria acervulina (EaGAPDH). Immunoblot analysis showed that recombinant EaGAPDH (rEaGAPDH) protein was successfully recognized by rat sera generated against rEaGAPDH. Interaction and internalisation of rEaGAPDH by chicken splenic-derived DCs (chSPDCs) was confirmed by immunofluorescence analysis. Flow cytometry revealed that chSPDCs upregulated MHCII, CD1.1, CD11c, CD80, and CD86 cell-surface markers. Moreover, mRNA expressions of DC maturation biomarkers (CCL5, CCR7, and CD83) and TLR signalling genes (TLR15 and MyD88) were also upregulated whereas those of Wnt signalling were non-significant compared to negative controls. rEaGAPDH treatment induced IL-12 and IFN-γ secretion in chSPDCs but had no effect on IL-10 and TGF-β. Likewise, DC-T cell co-culture promoted IFN-γ secretion and the level of IL-4 was unaffected. Proliferation of T cells and their differentiation into CD3+/CD4+ T cells were triggered in chSPDCs-T cells co-culture system. Taken together, rEaGAPDH could promote Th1 polarization by activating both host DCs and T cells and sheds new light on the role of this important molecule which might contribute to the development of new DCs-based immunotherapeutic strategies against coccidiosis.

Interleukin-12 Gene Expression into Acute Myeloid Leukemia-Derived Dendritic Cells Overcomes T-Cell Functional Impairment Induced by Leukemic Microenvironment.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1816-1816
Author(s):  
Antonio Curti ◽  
Simona Pandolfi ◽  
Michela Aluigi ◽  
Alessandro Isidori ◽  
Isabella Alessandrini ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Dendritic Cells ◽  
T Cell ◽  
Myeloid Leukemia ◽  
Interleukin 12 ◽  
Functional Features ◽  
Ifn Γ ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) cells are poorly immunogenic and release soluble factors inhibiting T-cell function. AML-derived dendritic cells (AML-DCs) have better antigen presentation capacity than leukemic blasts but share with AML cells some immunosuppressive features. In this study, we show that AML-DCs generated from CD14− AML samples (which represent 80% of total AML patients) are defective in IL-12 production. We, then, transfected CD14−-derived AML-DCs with IL-12 gene through the novel non-viral method nucleofection. IL-12 gene-nucleofected AML-DCs produce significant amount of IL-12 while maintain leukemia-specific karyotype, DC-like phenotype and function. In presence of the supernatant from the human leukemic cell line K562, allogeneic T-cell proliferation and interferon (IFN)-γ production induced by mock-transduced AML-DCs are significantly reduced. This effect is mainly directed on T cells, since AML-DC phenotype and cytokine production are not affected by leukemic supernatant. However, when stimulated by IL-12-producing AML-DCs, T cells produce higher concentrations of IFN-γ, thus maintaining a Th1 cytokine profile. In conclusion, IL-12 gene can be expressed into AML-DCs defective in endogenous IL-12 production by using a novel non-viral method which does not modify their phenotypical, cytogenetic and functional features. IL-12 gene expression into AML-DC counteracts the inhibitory effect of leukemic microenvironment on T lymphocytes

Potential Tolerizing Capacity of Human Dendritic Cells Featuring High Levels of Expression and Activity of the Tryptophan Metabolizing Enzyme Indoleamine 2,3 Dioxygenase.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 623-623
Author(s):  
Andreas Heitger ◽  
Birgit Juergens ◽  
Ursula Hainz ◽  
Dietmar Fuchs
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Fraction ◽  
Cell Responses ◽  
Indoleamine 2,3 Dioxygenase ◽  
Ifn Γ ◽  
Human Dendritic Cells ◽  
Expression And Activity

Abstract An enhanced tryptophan metabolism mediated by the enzymatic activity of indoleamine 2,3 dioxygenase (IDO) has recently been demonstrated to profoundly affect T cell responses. By the present study we explored whether human dendritic cells (DCs) displaying high IDO expression and activity, down-regulate allogeneic T cell responses. A comparison of lipopolysaccaride (LPS), interferon-γ (IFN-γ), and CD40L as DC maturation agents showed that most abundant IDO expression and activity in DCs was observed when immature DCs were exposed to a combination of LPS and IFN-γ for 48 hours. This time period of maturation was associated with the development of a mature DC phenotype. In contrast, semi-mature DCs, i.e. DCs matured for 4 hours only, were IDO negative. In co-cultures with allogeneic T cells both types of DCs began to metabolize tryptophan, as determined by decreasing concentrations of tryptophan and increasing concentrations of kynurenines in cell culture supernatants, but mature IDO positive DCs did so at a faster rate (complete consumption of tryptophan within 16 hours of co-culture) than semi-mature DCs. A comparison of the allo-stimulatory capacity of semi-mature IDO negative DCs and mature IDO positive DCs showed that at a high DC/T cell ratio (1:1) IDO positive DCs had a significantly reduced capacity to stimulate allogeneic T cells (median 63% reduction, n=5). The reduction of the allogeneic T cell response induced by IDO positive DCs was reversed upon the addition of the IDO inhibitor methylhydantoin-tryptophan to the co-cultures, suggesting an IDO dependent mechanism. Furthermore, allogeneic T cells exposed to IDO positive DCs had an increased rate of apoptosis in the activated cell fraction and after 8 days of co-culture contained a cell fraction (~30%) displaying a CD4+CD25+highFOXP3+ phenotype. These latter cells, when enriched by fluorescent activated cell sorting (FACS), were able to suppress the proliferative response of naive T cells to anti-CD3 mediated stimulation, which indicates the generation of a regulatory T cell population by IDO positive DCs. Together, these findings suggest that the amount of IDO expression and activity by DCs is one feature to govern the type of response of stimulated T cells. Human DCs can be induced to display high levels of IDO expression and activity and, thereby, acquire the ability to effectivley modulate allogeneic T cell responses towards tolerance by eliminating allo-reactive T cells through apoptosis and augmentation of their regulatory rather than their effector potential. Our current approaches address whether this property can be employed to use DCs for the generation of allo-antigen specific tolerance in the setting of hematopoietic cell transplantation.

scholarly journals Fimbriated Porphyromonas gingivalis Is More Efficient than Fimbria-Deficient P. gingivalis in Entering Human Dendritic Cells In Vitro and Induces an Inflammatory Th1 Effector Response

2004 ◽  
Vol 72 (3) ◽  
pp. 1725-1732 ◽  
Author(s):  
Ravi Jotwani ◽  
Christopher W. Cutler
Keyword(s):  
Dendritic Cells ◽  
Porphyromonas Gingivalis ◽  
Cell Metabolism ◽  
Necrosis Factor Alpha ◽  
Immature Dendritic Cells ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Gingival Mucosa ◽  
Human Dendritic Cells

ABSTRACT Porphyromonas gingivalis is a fimbriated mucosal pathogen implicated in chronic periodontitis (CP). The fimbriae are required for invasion of the gingival mucosa and for induction of CP in animal models of periodontitis. CP is associated with infection of immature dendritic cells (DCs) by P. gingivalis in situ and with increased numbers of dermal DCs (DDCs) and mature DCs in the lamina propria. The role of fimbriae in gaining entry into human DCs and how this modulates the inflammatory and effector immune responses, however, have not been explored. To address this, we generated monocyte-derived DCs (MDDCs) in vitro which phenotypically and functionally resemble DDCs. We show here that virulent fimbriated P. gingivalis 381, in contrast to its fimbria-deficient mutant, P. gingivalis DPG3, efficiently gains entry to MDDCs in a manner dependent on active cell metabolism and cytoskeletal rearrangement. In addition, uptake of 381, unlike DPG3, induces DCs to undergo maturation, upregulate costimulatory molecules, and secrete inflammation cytokines interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha, IL-10, and IL-12. Moreover, MDDCs pulsed with 381 also stimulated a higher autologous mixed lymphocyte reaction and induced a Th1-type response, with gamma interferon (IFN-γ) being the main cytokine. Monocytes used as controls demonstrated fimbria-dependent uptake of 381 as well but produced low levels of inflammatory cytokines compared to MDDCs. When MDDCs were pulsed with recombinant fimbrillin of P. gingivalis (10 μg/ml), maturation of MDDCs was also induced; moreover, matured MDDCs induced proliferation of autologous CD4+ T cells and release of IFN-γ. Thus, these results establish the significance of P. gingivalis fimbriae in the uptake of P. gingivalis by MDDCs and in induction of immunostimulatory Th1 responses.

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