CXCL14 Acts as a Specific Carrier of CpG DNA into Dendritic Cells and Activates Toll-like Receptor 9-mediated Adaptive Immunity

Tanegashima, Kosuke; Takahashi, Rena; Nuriya, Hideko; Iwase, Rina; Naruse, Naoto; Tsuji, Kohei; Shigenaga, Akira; Otaka, Akira; Hara, Takahiko

doi:10.1016/j.ebiom.2017.09.012

Cited by 21 publications

(31 citation statements)

References 38 publications

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“…After tissue infiltration, IL-15 may help promote T-cell survival [30] and effector function by upregulating IFN-γ production [31] and decreasing IL-17A expression [32]. Priming of these effector Th1 responses may be aided by CXCL14 that is chemotactic for dendritic cells [33] and transports CpG oligodeoxynucleotides into endosomes for Toll-like receptor 9 stimulation [34], which subsequently leads to the development of Th1 responses [35]. This is consistent with the increased frequency of effector memory Th1 cells reported in CXCL14-transgenic mice [36].…”

Section: Discussionmentioning

confidence: 99%

Cervical Cytokines Associated With Chlamydia trachomatis Susceptibility and Protection

Poston

Lee

Darville

et al. 2019

The Journal of Infectious Diseases

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Background. Chlamydia trachomatis can cause reproductive morbidities after ascending to the upper genital tract of women, and repeated infection can lead to worse disease. Data related to protective immune responses at the cervical mucosa that could limit chlamydial infection to the cervix and/or prevent reinfection inform vaccine approaches and biomarkers of risk. Methods. We measured 48 cytokines in cervical secretions from women having chlamydial cervical infection alone (n = 92) or both cervical and endometrial infection (n = 68). Univariable regression identified cytokines associated with differential odds of endometrial infection and reinfection risk, and multivariable stepwise regression identified cytokine ratios associated with differential risk. Results. Elevated interleukin (IL) 15/CXCL10 (odds ratio [OR], 0.55 [95% confidence interval {CI}, .37-.78]), IL-16/tumor necrosis factor-α (OR, 0.66 [95% CI, .45-.93]), and CXCL14/IL-17A (OR, 0.73 [95% CI, .54-.97]) cytokine ratios were significantly (P ≤ .05) associated with decreased odds of endometrial infection. A higher Flt-3L/IL-14 ratio was significantly (P = .001) associated with a decreased risk of reinfection (hazard ratio, 0.71 [95% CI, .58-.88]). Conclusions. Cytokines involved in humoral, type I interferon, and T-helper (Th) 17 responses were associated with susceptibility to C. trachomatis, whereas cytokines involved in Th1 polarization, recruitment, and activation were associated with protection against ascension and reinfection.

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Section: Discussionmentioning

confidence: 99%

Cervical Cytokines Associated With Chlamydia trachomatis Susceptibility and Protection

Poston

Lee

Darville

et al. 2019

The Journal of Infectious Diseases

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“…However, subsequent studies have shown that CXCL14 may not directly affect CXCR4 [ 86 ]. Other studies have shown that the receptors for CXCL14 may be G-protein coupled receptor 85 (GPR85) [ 87 ], toll-like receptor (TLR)9 after the formation of a complex of CXCL14 with CpG oligodeoxynucleotide [ 88 ], and insulin-like growth factor I receptor (IGF-IR) [ 89 ].…”

Section: CXC Chemokines In Cancermentioning

confidence: 99%

The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature

Korbecki

Kojder

Kapczuk

et al. 2021

IJMS

145

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Hypoxia is an integral component of the tumor microenvironment. Either as chronic or cycling hypoxia, it exerts a similar effect on cancer processes by activating hypoxia-inducible factor-1 (HIF-1) and nuclear factor (NF-κB), with cycling hypoxia showing a stronger proinflammatory influence. One of the systems affected by hypoxia is the CXC chemokine system. This paper reviews all available information on hypoxia-induced changes in the expression of all CXC chemokines (CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8 (IL-8), CXCL9, CXCL10, CXCL11, CXCL12 (SDF-1), CXCL13, CXCL14, CXCL15, CXCL16, CXCL17) as well as CXC chemokine receptors—CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7 and CXCR8. First, we present basic information on the effect of these chemoattractant cytokines on cancer processes. We then discuss the effect of hypoxia-induced changes on CXC chemokine expression on the angiogenesis, lymphangiogenesis and recruitment of various cells to the tumor niche, including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), regulatory T cells (Tregs) and tumor-infiltrating lymphocytes (TILs). Finally, the review summarizes data on the use of drugs targeting the CXC chemokine system in cancer therapies.

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“…Using the same end-point RT.PCR stratagem, we have reported a similar expression profile for the Ifnγ and inducible ligand genes Cxcl 9, Cxcl 10 and Cxcl 11 and its shared receptor gene Cxcr 3 to that reported in the infected brains of a rat model of HAT [ 34 ]. In contrast to the other Cxcl mRNAs, Cxcl 14 had a Stage 1 [7dpi↑] signature while a recent study found that the pleiotropic CXCL14 specifically binds to CpG DNA and activates TLR9 on macrophages, thereby inducing inflammatory cytokines [ 76 ]. This expression signature was compared ( Table 5 ) with a compilation profile of Ccl and Cxcl ligand genes expressed in infected rodent brains [ 3 ].…”

Section: Resultsmentioning

confidence: 99%

Microarray profiling predicts early neurological and immune phenotypic traits in advance of CNS disease during disease progression in Trypanosoma. b. brucei infected CD1 mouse brains

Montague

Bradley

Rodgers³

et al. 2021

PLoS Negl Trop Dis

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Human African trypanosomiasis (HAT), also known as sleeping sickness, is a major cause of mortality and morbidity in sub-Saharan Africa. We hypothesised that recent findings of neurological features and parasite brain infiltration occurring at much earlier stages in HAT than previously thought could be explained by early activation of host genetic programmes controlling CNS disease. Accordingly, a transcriptomal analysis was performed on brain tissue at 0, 7, 14, 21 and 28dpi from the HAT CD1/GVR35 mouse model. Up to 21dpi, most parasites are restricted to the blood and lymphatic system. Thereafter the trypanosomes enter the brain initiating the encephalitic stage. Analysis of ten different time point Comparison pairings, revealed a dynamic transcriptome comprising four message populations. All 7dpi Comparisons had by far more differentially expressed genes compared to all others. Prior to invasion of the parenchyma, by 7dpi, ~2,000 genes were up-regulated, denoted [7dpi↑] in contrast to a down regulated population [7dpi↓] also numbering ~2,000. However, by 14dpi both patterns had returned to around the pre-infected levels. The third, [28dpi↑] featured over three hundred transcripts which had increased modestly up to14dpi, thereafter were significantly up-regulated and peaked at 28dpi. The fourth, a minor population, [7dpi↑-28dpi↑], had similar elevated levels at 7dpi and 28dpi. KEGG and GO enrichment analysis predicted a diverse phenotype by 7dpi with changes to innate and adaptive immunity, a Type I interferon response, neurotransmission, synaptic plasticity, pleiotropic signalling, circadian activity and vascular permeability without disruption of the blood brain barrier. This key observation is consistent with recent rodent model neuroinvasion studies and clinical reports of Stage 1 HAT patients exhibiting CNS symptoms. Together, these findings challenge the strict Stage1/Stage2 phenotypic demarcation in HAT and show that that significant neurological, and immune changes can be detected prior to the onset of CNS disease.

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CXCL14 Acts as a Specific Carrier of CpG DNA into Dendritic Cells and Activates Toll-like Receptor 9-mediated Adaptive Immunity

Cited by 21 publications

References 38 publications

Cervical Cytokines Associated With Chlamydia trachomatis Susceptibility and Protection

Cervical Cytokines Associated With Chlamydia trachomatis Susceptibility and Protection

The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature

Microarray profiling predicts early neurological and immune phenotypic traits in advance of CNS disease during disease progression in Trypanosoma. b. brucei infected CD1 mouse brains

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