Unique functions of splenic CD8α+ dendritic cells during infection with intracellular pathogens

Neuenhahn, Michael; Busch, Dirk H.

doi:10.1016/j.imlet.2007.09.007

Cited by 33 publications

(29 citation statements)

References 75 publications

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“…Once localized within the draining LNs, mobilized DCs migrate to T cell-rich areas via a CCR7-dependent process, where they present Ag peptides to responsive CD4 ϩ T cells or transfer their cargo to LN-resident CD8␣ ϩ DCs for subsequent presentation to CD8 ϩ T cells (21)(22)(23). Following selected types of stimulant-induced activation, however, many immature myeloid DCs that become mobilized from vaccination sites bypass sequestration in the draining LN, and gain the capacity to localize into any secondary lymphoid organ or the bone marrow (10,13,24,25).…”

Section: Cd11bmentioning

confidence: 99%

TLR-Induced Local Metabolism of Vitamin D3 Plays an Important Role in the Diversification of Adaptive Immune Responses

Enioutina

Bareyan

Daynes

2009

The Journal of Immunology

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The addition of monophosphoryl lipid A, a minimally toxic derivative of LPS, to nonmucosally administered vaccines induced both systemic and mucosal immune responses to coadministered Ags. This was dependent on an up-regulated expression of 1α-hydroxylase (CYP27B1, 1αOHase), the enzyme that converts 25-hydroxycholecalciferol, a circulating inactive metabolite of vitamin D3, into 1,25(OH)2D3 (calcitriol). In response to locally produced calcitriol, myeloid dendritic cells (DCs) migrated from cutaneous vaccination sites into multiple secondary lymphoid organs, including classical inductive sites of mucosal immunity, where they effectively stimulated B and T cell immune responses. The endogenous production of calcitriol by monophosphoryl lipid A-stimulated DCs appeared to be Toll-IL-1R domain-containing adapter-inducing IFN-β-dependent, mediated through a type 1 IFN-induced expression of 1αOHase. Responsiveness to calcitriol was essential to promote the trafficking of mobilized DCs to nondraining lymphoid organs. Collectively, these studies help to expand our understanding of the physiologically important roles played by locally metabolized vitamin D3 in the initiation and diversification of adaptive immune responses. The influences of locally produced calcitriol on the migration of activated DCs from sites of vaccination/infection into both draining and nondraining lymphoid organs create a condition whereby Ag-responsive B and T cells residing in multiple lymphoid organs are able to simultaneously engage in the induction of adaptive immune responses to peripherally administered Ags as if they were responding to an infection of peripheral or mucosal tissues they were designed to protect.

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Section: Cd11bmentioning

confidence: 99%

TLR-Induced Local Metabolism of Vitamin D3 Plays an Important Role in the Diversification of Adaptive Immune Responses

Enioutina

Bareyan

Daynes

2009

The Journal of Immunology

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“…The quality and quantity of induced immune responses are primarily dependent upon the activation state of the DCs (1-2,7). Immature DCs present antigens to T cells in the absence of appropriate co-stimulation leading to tolerance, while the mature DCs display unique properties that trigger the antigen-specific immunity (1,(7)(8)(9). Maturation of DCs is associated with an enhanced expression of co-stimulatory molecules CD40, CD80, CD86 and several members of the tumor necrosis factor (TNF)/TNF-receptor family including the CD70 (ligand for CD27) as well as with an elevated expression of MHC I and II molecules on DCs which in turn acquire an increased ability to present tumor antigens to T and B effector cells (2,10).…”

Section: Introductionmentioning

confidence: 99%

“…Maturation of DCs is associated with an enhanced expression of co-stimulatory molecules CD40, CD80, CD86 and several members of the tumor necrosis factor (TNF)/TNF-receptor family including the CD70 (ligand for CD27) as well as with an elevated expression of MHC I and II molecules on DCs which in turn acquire an increased ability to present tumor antigens to T and B effector cells (2,10). It is well recognized that 'danger' signals are essential pre-requisites for the maturation and activation of DCs into powerful antigen presenting cells (9)(10)(11)(12). By mimicking bacterial DNA synthetic CpG oligodeoxynucletides (CpG ODN) act as danger signals and have been shown to stimulate maturation of DCs via the Toll-like receptor 9 (TLR9) (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Tumor vaccine composed of CpG ODN class C and irradiated tumor cells up-regulates the expression of genes characteristic of mature dendritic cells and of memory cells

Novaković

2011

Int J Oncol

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Abstract. Only properly mature dendritic cells (DCs) in the presence of tumor antigens accomplish to activate all of the elements of the immune network and have the potential to induce tumor-specific effectors and memory T cells. In the current study, we firstly aimed to investigate the in vivo maturation of antigen presenting cells (APCs) at the molecular level by following the expression of CD11c, CD86 and MyD88 genes in the mixture of mononuclear cells after treatment of mice with a tumor vaccine composed of C-class CpG oligodeoxynucletides (CpG ODN) and irradiated melanoma B16F1 tumor cells. The second objective was to define whether the tumor vaccine induces generation of memory T cells (CD44 hi CD62L lo/hi CD27 hi ). Finally, based on gene expression pattern we aimed to determine the tissue distribution and homing of the (mature) APCs and memory cells after vaccination. We demonstrated that by tumor vaccine the APCs (including DCs) are manipulated in vivo. By this kind of vaccine, the differentiation and maturation of APCs is triggered primarily in the spleen and is subsequently followed by the migration of these APCs to the bone marrow. Once in the bone marrow, these APCs play a crucial role in the development and maintenance of long-lived memory T cells capable of preventing a relapse of malignant disease. In conclusion, our results provide insight into the nature and scope of the antitumor immune response elicited by this kind of tumor vaccine in vivo. We showed that the maturation of APCs is a prerequisite for the generation of effective longterm antitumor immunity.

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“…Mouse studies typically employ intravenous injection of Listeria, which results in systemic infection 2 . After injection, Listeria quickly disseminates to the spleen and liver due to uptake by CD8α + dendritic cells and Kupffer cells 3,4 . .…”

mentioning

confidence: 99%

“…After injection, Listeria quickly disseminates to the spleen and liver due to uptake by CD8α + dendritic cells and Kupffer cells 3,4 . Once phagocytosed, various bacterial proteins enable Listeria to escape the phagosome, survive within the cytosol, and infect neighboring cells 5 .…”

mentioning

confidence: 99%

Measuring Bacterial Load and Immune Responses in Mice Infected with <em>Listeria monocytogenes</em>

Wang

Strugnell

Wijburg

et al. 2011

JoVE

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Listeria monocytogenes (Listeria) is a Gram-positive facultative intracellular pathogen 1 . Mouse studies typically employ intravenous injection of Listeria, which results in systemic infection 2 . After injection, Listeria quickly disseminates to the spleen and liver due to uptake by CD8α + dendritic cells and Kupffer cells 3,4 . . Generally, mice with increased susceptibility to Listeria infection are less able to control bacterial proliferation, demonstrating increased bacterial load and/or delayed clearance compared to resistant mice. Genetic studies, including linkage analyses and knockout mouse strains, have identified various genes for which sequence variation affects host responses to Listeria infection 6,[8][9][10][11][12][13][14] . Determination and comparison of infection kinetics between different mouse strains is therefore an important method for identifying host genetic factors that contribute to immune responses against Listeria. Comparison of host responses to different Listeria strains is also an effective way to identify bacterial virulence factors that may serve as potential targets for antibiotic therapy or vaccine design.We describe here a straightforward method for measuring bacterial load (colony forming units [CFU] per tissue) and preparing single-cell suspensions of the liver and spleen for FACS analysis of immune responses in Listeria-infected mice. This method is particularly useful for initial characterization of Listeria infection in novel mouse strains, as well as comparison of immune responses between different mouse strains infected with Listeria. We use the Listeria monocytogenes EGD strain 15 that, when cultured on blood agar, exhibits a characteristic halo zone around each colony due to β-hemolysis 1 (Figure 1). Bacterial load and immune responses can be determined at any time-point after infection by culturing tissue homogenate on blood agar plates and preparing tissue cell suspensions for FACS analysis using the protocols described below. We would note that individuals who are immunocompromised or pregnant should not handle Listeria, and the relevant institutional biosafety committee and animal facility management should be consulted before work commences. Video LinkThe video component of this article can be found at https://www.jove.com/video/3076/ Protocol 1. Culturing and long-term storage of Listeria monocytogenes (Listeria)1. Make or purchase pre-made horse blood agar (HBA) plates. Dry plates prior to use by pre-incubating at 37°C overnight or placing uncovered in a laminar flow cabinet for 1 hour. 2. Obtain viable Listeria from one of the following: an infected mouse tissue homogenate, a lyophilized stock, a frozen glycerol stock, or a colony from a recent Listeria culture (i.e. less than one-week old and not sub-cultured more than 10 generations). All Listeria should be obtained using a sterile inoculating loop and employing aseptic techniques for all methods described in this protocol. 3. Streak Listeria on a HBA plate as shown in Figure 1 using a sterile ino...

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Unique functions of splenic CD8α+ dendritic cells during infection with intracellular pathogens

Cited by 33 publications

References 75 publications

TLR-Induced Local Metabolism of Vitamin D3 Plays an Important Role in the Diversification of Adaptive Immune Responses

TLR-Induced Local Metabolism of Vitamin D3 Plays an Important Role in the Diversification of Adaptive Immune Responses

Tumor vaccine composed of CpG ODN class C and irradiated tumor cells up-regulates the expression of genes characteristic of mature dendritic cells and of memory cells

Measuring Bacterial Load and Immune Responses in Mice Infected with <em>Listeria monocytogenes</em>

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