Dendritic Cells Stimulated with<i>Actinobacillus actinomycetemcomitans</i>Elicit Rapid Gamma Interferon Responses by Natural Killer Cells

Kikuchi, Takeshi; Hahn, Chin‐Lo; Tanaka, Sho; Barbour, Suzanne E.; Schenkein, Harvey A.; Tew, John G.

doi:10.1128/iai.72.9.5089-5096.2004

Cited by 68 publications

(97 citation statements)

References 45 publications

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“…Interleukin 12 (IL-12) is one of the factors known to mediate DC-NK cell cross talk and was previously reported to be secreted by DCs infected with either A. actinomycetemcomitans or P. gingivalis (15,16). Indeed, IL-12 was able to trigger CRACC induction on primary human NK cells in a dose-dependent manner (Fig.…”

Section: Resultsmentioning

confidence: 87%

“…IFN-␥ production by NK cells was shown to be triggered by coculture with dendritic cells (DCs) stimulated with P. gingivalis (15) or A. actinomycetemcomitans (16). A recent study reported that the periodontal pathogen Fusobacterium nucleatum is directly recognized by the NK cell-activating receptor NKp46 and that NK cell activation is associated with periodontal bone loss in vivo (17).…”

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confidence: 99%

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Role of the NK Cell-Activating Receptor CRACC in Periodontitis

et al. 2013

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Periodontitis is a highly prevalent, biofilm-mediated chronic inflammatory disease that results in the loss of the tooth-supporting tissues. It features two major clinical entities: chronic periodontitis, which is more common, and aggressive periodontitis, which usually has an early onset and a rapid progression. Natural killer (NK) cells are a distinct subgroup of lymphocytes that play a major role in the ability of the innate immune system to steer immune responses. NK cells are abundant in periodontitis lesions, and NK cell activation has been causally linked to periodontal tissue destruction. However, the exact mechanisms of their activation and their role in the pathophysiology of periodontitis are elusive. Here, we show that the predominant NK cellactivating molecule in periodontitis is CD2-like receptor activating cytotoxic cells (CRACC). We show that CRACC induction was significantly more pronounced in aggressive than chronic periodontitis and correlated positively with periodontal disease severity, subgingival levels of specific periodontal pathogens, and NK cell activation in vivo. We delineate how Aggregatibacter actinomycetemcomitans, an oral pathogen that is causally associated with aggressive periodontitis, indirectly induces CRACC on NK cells via activation of dendritic cells and subsequent interleukin 12 (IL-12) signaling. In contrast, we demonstrate that fimbriae from Porphyromonas gingivalis, a principal pathogen in chronic periodontitis, actively attenuate CRACC induction on NK cells. Our data suggest an involvement of CRACC-mediated NK cell activation in periodontal tissue destruction and point to a plausible distinction in the pathobiology of aggressive and chronic periodontitis that may help explain the accelerated tissue destruction in aggressive periodontitis.

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Section: Resultsmentioning

confidence: 87%

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confidence: 99%

Role of the NK Cell-Activating Receptor CRACC in Periodontitis

et al. 2013

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“…It is interesting that in our separate study, hIL-4 injected into A. actinomycetemcomitans-infected HuPBL-NOD/SCID mice yielded a similar outcome where there was a concomitant lower frequency of RANKL ϩ Th cells coexpressing hIFN-␥ associated with decreased alveolar bone loss in vivo but no significant changes regarding IL-4 expression on RANKL ϩ Th cells (data not shown). It is possible that there are auxiliary regulations mediated by non-T-cell sources (i.e., B and NK cells) (6,15) or different cytokines (e.g., TNF-␣, IL-1, and IL-12) (26,31,36) that may contribute, in part, to the above phenomenon. In addition, the physiological function of RANKL ϩ Th cells coexpressing hIL-4 for bone loss in vivo remains unclear and might be redundant, as other cytokines, such as type I IFNs, IL-7, IL-12, IL-18, etc., can inhibit RANKL-mediated osteoclastogenesis (26,36).…”

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confidence: 99%

Interleukin-10 Inhibits Gram-Negative-Microbe-Specific Human Receptor Activator of NF-κB Ligand-Positive CD4 ⁺ -Th1-Cell- Associated Alveolar Bone Loss In Vivo

Zhang

Teng

2006

Infect Immun

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To study anti-inflammatory cytokine effects on RANKL؉ -T-cell-mediated osteoclastogenesis in vivo, we injected human interleukin-10 (hIL-10) into pathogen-infected HuPBL-NOD/SCID mice. The results show significantly decreased RANKL ؉ Th1-associated alveolar bone loss and coexpression of human gamma interferon (hIFN-␥) and human macrophage colony-stimulating factor, but not hIL-4, in RANKL ؉ Th cells compatible with those from successfully treated aggressive periodontitis subjects. Thus, there are critical cytokine interactions linking hIFN-␥ ؉ Th1 cells to RANKL-RANK/OPG signaling for periodontal osteoclastogenesis in vivo.

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“…In blood, or in sites infiltrated with blood, NK cells are the source of this rapid IFN-γ (24-hour) that promotes DC-IL-12. NK cells need IL-12 for Barbour et al (2002) optimal IFN-γ, and it appears that P. gingivalis-DC-NK interactions result in reciprocal activation and increased DC-IL-12 and NK cell-IFN-γ (Kikuchi et al, 2004(Kikuchi et al, , 2005(Kikuchi et al, , 2010. Both DCs and NK cells are necessary to get the rapid 24-hour IFN-γ needed to induce the P. gingivalis-specific IgG2 in recall responses in PBL cultures (Kikuchi et al, 2005).…”

Section: Pro-inflammatory Cytokines and Igg2 Responsesmentioning

confidence: 99%

“…Our major hypothesis was that α-PC/α-CL would promote pro-inflammatory cytokine production, including NK-cell-IFN-γ that is released by 24 to 48 hrs after engaging IL-12-producing DCs (Kikuchi et al, 2004). However, DC-IL-10 is anti-inflammatory, and the IL-12/IL-10 ratio is important in determining whether a given stimulus is pro-inflammatory or anti-inflammatory.…”

Section: Antibodies and Pro-inflammatory Cytokine Productionmentioning

confidence: 99%