Interleukin-10 Modulates Antigen Presentation by Dendritic Cells through Regulation of NLRP3 Inflammasome Assembly during Chlamydia Infection

Omosun, Yusuf; McKeithen, Danielle; Ryans, Khamia; Kibakaya, Caroline; Blás-Machado, Uriel; Li, Duo; Singh, Rajesh; Inoue, Kōichi; Xiong, Zhi Gang; Eko, Francis O.; Black, Carolyn M.; Igietseme, Joseph U.; He, Qing

doi:10.1128/iai.00993-15

Cited by 37 publications

(24 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The finding mentioned in the former study is supported at least partially by the observed inflammasome-mediated pyroptosis of Chlamydia -exposed antigen presentation cells, which are critical in Chlamydia clearance (38). However, a later study has its own limitations as the results were obtained in IL-10 −/− dendritic cells (DCs) and no direct observations were made in cells lacking inflammasome components.…”

Section: Chlamydia Infectionmentioning

confidence: 67%

Inflammasomes and Their Role in Innate Immunity of Sexually Transmitted Infections

et al. 2016

View full text Add to dashboard Cite

Inflammasomes are multiprotein complexes present in the cytosol as pattern recognition receptors or as sensors of damage-associated molecular patterns. After recognition of microbe-associated molecular patterns or host-derived danger signals, nucleotide oligomerization domain-like receptors oligomerize to form inflammasomes. The activation of inflammasomes results in an alarm, which is raised to alert adjacent cells through the processing and release of a number of other substrates present in the cytosol. A wide array of inflammasomes and their adapter molecules have been identified in the host’s innate immune system in response to various pathogens. Components of specific pathogens activate different inflammasomes, which once activated in response to pathogen-induced infection, induce the activation of caspases, and the release of mature forms of interleukin-1β (IL-1β) and IL-18. Identifying the mechanisms underlying pathogen-induced inflammasome activation is important if we are to develop novel therapeutic strategies to target sexually transmitted infections (STIs) related pathogens. This information is currently lacking in literature. In this review, we have discussed the role of various inflammasomes in sensing different STIs, as well as the beneficial or detrimental effects of inflammasome signaling in host resistance. Additionally, we have discussed both canonical and non-canonical processing of IL-1β induced with respect to particular infections. Overall, these findings transform our understanding of both the basic biology and clinical relevance of inflammasomes.

show abstract

Section: Chlamydia Infectionmentioning

confidence: 67%

Inflammasomes and Their Role in Innate Immunity of Sexually Transmitted Infections

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Those alterations in metabolism are required to meet the increased biosynthetic and bioenergetic demands of activated DCs specifically by funneling metabolites into pathways for lipid and protein synthesis [14, 30–33]. Disruption of glycolysis through the reduced expression of ENO1 has recently been linked to NLRP3 activation [23], and we have previously shown that NLRP3 inflammasome assembly was suppressed in IL-10 −/− DCs [18], which we now know to have abundantly expressed ENO1, this shows an interesting linkage of ENO1 to the inflammasome that would be explored further.…”

Section: Discussionmentioning

confidence: 99%

The immunoregulatory role of alpha enolase in dendritic cell function during Chlamydia infection

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundWe have previously reported that interleukin-10 (IL-10) deficient dendritic cells (DCs) are potent antigen presenting cells that induced elevated protective immunity against Chlamydia. To further investigate the molecular and biochemical mechanism underlying the superior immunostimulatory property of IL-10 deficient DCs we performed proteomic analysis on protein profiles from Chlamydia-pulsed wild-type (WT) and IL-10−/− DCs to identify differentially expressed proteins with immunomodulatory properties.ResultsThe results showed that alpha enolase (ENO1), a metabolic enzyme involved in the last step of glycolysis was significantly upregulated in Chlamydia-pulsed IL-10−/− DCs compared to WT DCs. We further studied the immunoregulatory role of ENO1 in DC function by generating ENO1 knockdown DCs, using lentiviral siRNA technology. We analyzed the effect of the ENO1 knockdown on DC functions after pulsing with Chlamydia. Pyruvate assay, transmission electron microscopy, flow cytometry, confocal microscopy, cytokine, T-cell activation and adoptive transfer assays were also used to study DC function. The results showed that ENO1 knockdown DCs had impaired maturation and activation, with significant decrease in intracellular pyruvate concentration as compared with the Chlamydia-pulsed WT DCs. Adoptive transfer of Chlamydia-pulsed ENO1 knockdown DCs were poorly immunogenic in vitro and in vivo, especially the ability to induce protective immunity against genital chlamydia infection. The marked remodeling of the mitochondrial morphology of Chlamydia-pulsed ENO1 knockdown DCs compared to the Chlamydia-pulsed WT DCs was associated with the dysregulation of translocase of the outer membrane (TOM) 20 and adenine nucleotide translocator (ANT) 1/2/3/4 that regulate mitochondrial permeability. The results suggest that an enhanced glycolysis is required for efficient antigen processing and presentation by DCs to induce a robust immune response.ConclusionsThe upregulation of ENO1 contributes to the superior immunostimulatory function of IL-10 deficient DCs. Our studies indicated that ENO1 deficiency causes the reduced production of pyruvate, which then contributes to a dysfunction in mitochondrial homeostasis that may affect DC survival, maturation and antigen presenting properties. Modulation of ENO1 thus provides a potentially effective strategy to boost DC function and promote immunity against infectious and non-infectious diseases.

show abstract

“…If correct, this hypothesis implies that C. trachomatis, like N. gonorrhoeae, has the ability to suppress or at least delay the onset of immune responses that might be effective against it, and that eventually the host immune system might break through and mount protective responses. IL-10 induced by Chlamydia has been found to modulate antigen-presentation by dendritic cells and drive them into a regulatory response mode, and in its absence, Chlamydia is more rapidly cleared (Omosun et al 2015).…”

Section: Chlamydiamentioning

confidence: 99%

Chlamydia Trachomatis Urogenital Infections

Armitage

Carey

Hickey

et al. 2018

Diagnostics to Pathogenomics of Sexually Transmitted Infections

View full text Add to dashboard Cite

Quantitative evaluation of the cells involved in the immune system, such as lymphocytes, plasma cells, macrophages, dendritic cells, and epithelial cells, together with their products, including antibodies, cytokines, and humoral factors of innate immunity, convincingly revealed that the immune system associated with the mucosae is greater than its systemic counterpart (Russell et al. 2015a). This fact should not be surprising, as the development of the entire immune system during evolution and continuously in everyday life is driven by stimulation with commensal microbiota, antigens present in food and inhaled air, as well as pathogens throughout the enormous surface area of mucosal sites, which far exceeds the skin surface. The mucosal immune system comprises anatomically remote and physiologically distinct compartments that provide protection at various mucosal sites. Although the genital tract shares some common features with other mucosae, including the presence of humoral factors and cells of innate immunity, and the origin of cells involved in antibody production and T cell-mediated immunity, there are also many distinct features characteristic of the genital tract (Russell and Mestecky 2002, 2010; Mestecky et al. 2005). The spectrum of antigens including commensal or pathogenic microorganisms, and sperm is different from those at other mucosal sites. Furthermore, the primary physiological role of the genital tract is reproduction, which involves the acceptance of allogeneic sperm and semi-allogeneic offspring. This distinct physiological role influences the immune system of the genital tract with respect to the induction or suppression of immune responses, which must be considered in the development and application of vaccines against infectious agents of sexually transmitted diseases.

show abstract

Interleukin-10 Modulates Antigen Presentation by Dendritic Cells through Regulation of NLRP3 Inflammasome Assembly during Chlamydia Infection

Cited by 37 publications

References 45 publications

Inflammasomes and Their Role in Innate Immunity of Sexually Transmitted Infections

Inflammasomes and Their Role in Innate Immunity of Sexually Transmitted Infections

The immunoregulatory role of alpha enolase in dendritic cell function during Chlamydia infection

Chlamydia Trachomatis Urogenital Infections

Contact Info

Product

Resources

About