Dendritic Cells: Immune Saviors or Achilles' Heel?

Cutler, Christopher W.; Jotwani, Ravi; Pulendran, Bali

doi:10.1128/iai.69.8.4703-4708.2001

Cited by 37 publications

(52 citation statements)

References 102 publications

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“…Cell surface oligosaccharides also facilitate the phagocytosis of oral bacteria by antigen-presenting cells, such as macrophages and immature MDDC. MDDC are especially well suited for the uptake of oral bacteria as they express a family of pattern recognition receptors that recognize microbial carbohydrates (1,9). Indeed, Cutler et al have recently demonstrated that P. gingivalis is readily phagocytosed by immature dendritic cells both in vitro and in vivo and that uptake of P. gingivalis induces dendritic cell maturation (8).…”

Section: Discussionmentioning

confidence: 99%

“…Immature MDDC express high levels of class II major histocompatibility complex (MHC) proteins and costimulatory molecules and hence are very potent antigen-presenting cells (1) (9). In addition, MDDC express a variety of pattern recognition receptors and hence are well adapted for uptake and processing of oral pathogens, such as P. gingivalis and A. acti- nomycetemcomitans (1,9). In this study, we demonstrated that the MDDC induce IgG2 in a PWM-driven system, and this suggests that MDDC also have antigen-independent effects on the production of IgG2.…”

Section: Discussionmentioning

confidence: 99%

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Monocyte Differentiation in Localized Juvenile Periodontitis Is Skewed toward the Dendritic Cell Phenotype

et al. 2002

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Several lines of evidence indicate that the monocytes of subjects with localized juvenile periodontitis (LJP) are functionally distinct from cells of age-and race-matched nonperiodontitis (NP) subjects. Among the abnormalities are the propensity to secrete large amounts of prostaglandin E 2 and the induction of immunoglobulin G2 (IgG2) antibodies. The experiments described here were performed to further characterize the LJP monocytes and to determine if these cells mature differently than NP monocytes. When adherent monocytes from LJP subjects were cultured in the presence of human serum, both macrophages and cells with the morphology of immature monocyte-derived dendritic cells (MDDC) were observed. Within 4 days the prevalence of the immature MDDC was approximately twofold higher in LJP cultures than in NP cultures. In addition to their dendritic morphology, these cells were CD11c ؉ and CD14 ؊ or CD14 low and stimulated potent autologous mixed leukocyte reactions, consistent with differentiation to the MDDC phenotype. Like LJP monocytes, cultures of MDDC generated with interleukin-4 and granulocyte-macrophage colony-stimulating factor selectively induced IgG2 in cultures of pokeweed mitogen-stimulated NP leukocytes. Together, these data suggest that the monocytes of LJP subjects have a propensity to differentiate into MDDC and that this differentiation may be related to the high levels of IgG2 that are observed in the sera of LJP subjects. As high levels of circulating IgG2 are correlated with less severe disease, the propensity of LJP monocytes to differentiate into MDDC may have important implications for both the host response against oral pathogens and the progression of LJP.Localized juvenile periodontitis (LJP) is a form of earlyonset periodontitis that tends to run in families. Several oral pathogens have been linked to the etiology of the disease, including Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis (4,22,36,37). However, mounting evidence suggests that alterations in the host response may contribute to the pathogenesis of LJP. Several studies have highlighted abnormalities in the myeloid compartment of LJP subjects. For example, LJP neutrophils exhibit reduced chemotactic and calcium responses (7, 10) and have altered diacylglycerol metabolism (32) compared to cells from nonperiodontitis (NP) individuals. The peripheral blood of LJP subjects contains abnormally large numbers of immature granulocytes, which express low levels of CD16 (25). It also appears that the monocytes of LJP subjects are somewhat abnormal, as these cells produce abnormally large amounts of prostaglandin E 2 (PGE 2 ) in response to stimulation with lipopolysaccharide (26, 30). Our group has been particularly intrigued by the unique relationship that appears to exist between LJP monocytes and antibody production.LJP patients exhibit elevated levels of circulating immunoglobulin G2 (IgG2) compared to age-and race-matched NP subjects (23). In contrast, the levels of other isotypes of IgG are similar in NP and L...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Monocyte Differentiation in Localized Juvenile Periodontitis Is Skewed toward the Dendritic Cell Phenotype

et al. 2002

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“…A strong Th1 T-cell component has been described and has been implicated in perpetuating the inflammatory changes that lead to disease (18). Recent evidence indicates that antigen presentation by dendritic cells is required to initiate a primary Th1 T-cell immune response (5,12). Furthermore, the Th1-biased response is facilitated by IL-12 elaboration in the context of the antigen presentation process.…”

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confidence: 99%

Helicobacter pyloriPreferentially Induces Interleukin 12 (IL-12) Rather than IL-6 or IL-10 in Human Dendritic Cells

2003

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Dendritic cells are potent antigen-presenting cells that are present in the gastrointestinal tract and are required for the induction of a Th1 T-cell acquired immune response. Since infection with the gastric pathogen Helicobacter pylori elicits a Th1 cell response, the interaction of these organisms with dendritic cells should reflect the Th1 bias. We incubated H. pylori with cultured human dendritic cells and measured the cytokine induction profile, comparing the response to that induced by Salmonella enterica serovar Typhimurium. We found that H. pylori induced little interleukin 6 (IL-6) and essentially no IL-10 in contrast to S. enterica. However, H. pylori induced levels of IL-12 that were 30% of those induced by S. enterica, indicating a Th1 response. An isogenic cagE mutant of H. pylori lost about 50% of its IL-12-inducing ability, suggesting a role for the cag type IV secretion system in the stimulation of dendritic cells.

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“…Ni 2+ penetrates the skin and activates epithelial cells that produce cytokines or chemokines following hyperreactive immune responses involving the activation of APCs and T cells (13)(14)(15). APCs, such as Langerhans cells or dendritic cells (DCs), are induced by certain cytokines, including IL-1b and TNF-a, which are produced by epithelial cells (16)(17)(18)(19). APCs migrate to draining lymph nodes where they present allergens or haptens to naive T cells.…”

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confidence: 99%

A Critical Role for Thymic Stromal Lymphopoietin in Nickel-Induced Allergy in Mice

Ashrin

Arakaki

Yamada

et al. 2014

The Journal of Immunology

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Ni is the most frequent cause of contact allergy induced by metals. However, the underlying mechanism of this induction is unknown. Our previous research demonstrates that activation of dendritic cells (DCs) through p38MAPK/MKK6 is required for Ni-induced allergy in mice. In the current study, we investigated the cellular and molecular mechanisms underlying Ni-induced allergy using a mouse model that involves injecting Ni into the ear, with or without Freund’s incomplete or complete adjuvants. Nickel had greater potential to cause allergic reactions compared with palladium and gold. Among the proteins expressed at higher levels in mice with Ni-induced allergy, we focused on thymic stromal lymphopoietin (TSLP), which is produced in abundance by keratinocytes. We detected increased expression of the TSLP receptor (TSLPR) in DCs from cervical lymph nodes of mice with Ni-induced allergy, suggesting that DCs in ear tissues were activated through TSLPR signaling induced by keratinocyte-derived TSLP. Furthermore, delayed-type hypersensitivity reactions in mice with Ni-induced allergy were decreased significantly by injection of a Tslp–short interfering RNA along with atelocollagen in the ear skin. These results suggest that Ni allergy may be triggered by a TSLP/TSLPR-mediated interaction between epithelial and immune cells.

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Dendritic Cells: Immune Saviors or Achilles' Heel?

Cited by 37 publications

References 102 publications

Monocyte Differentiation in Localized Juvenile Periodontitis Is Skewed toward the Dendritic Cell Phenotype

Monocyte Differentiation in Localized Juvenile Periodontitis Is Skewed toward the Dendritic Cell Phenotype

Helicobacter pyloriPreferentially Induces Interleukin 12 (IL-12) Rather than IL-6 or IL-10 in Human Dendritic Cells

A Critical Role for Thymic Stromal Lymphopoietin in Nickel-Induced Allergy in Mice

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