TLR9 is expressed in human papillomavirus-positive cervical cells and is overexpressed in persistent infections

Cannella, Fabiana; Pierangeli, Alessandra; Scagnolari, Carolina; Cacciotti, Giulia; Tranquilli, Giulia; Stentella, P; Recine, Nadia; Antonelli, Guido

doi:10.1016/j.imbio.2014.10.012

Cited by 40 publications

(24 citation statements)

References 38 publications

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“…Moreover, HPV‐16 may interfere with these responses, thus enhancing their persistence . In this study, TLR9 expression was upregulated during high‐risk HPV infection and was higher in HPV‐positive compared to HPV‐negative individuals, confirming that TLR9 plays an important role in the detection of CpG islands in the DNA motifs during HPV infection in vivo .…”

Section: Discussionsupporting

confidence: 63%

Mechanisms of sexually transmitted infection‐induced inflammation in women: implications for HIV risk

et al. 2019

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Introduction Globally, sexually transmitted infections (STI) affect >300 million people annually, and are a major cause of sexual and reproductive health complications in women. In this commentary, we describe how STIs interact with the immune and non‐immune cells, both within and below the cervicovaginal mucosal barrier, to cause inflammation, which in turn has been associated with increased HIV acquisition risk. Discussion STIs have a major impact on the female genital mucosa, which is an important biological and physical barrier that forms the first line of defence against invading microorganisms such as HIV. Pattern recognition of STI pathogens, by receptors expressed either on the cell surface or inside the cell, typically triggers inflammation at the mucosal barrier. The types of mucosal responses vary by STI, and can be asymptomatic or culminate in the formation of discharge, ulcers and/or warts. While the aim of this response is to clear the invading microbes, in many cases these responses are either evaded or cause pathology that impairs barrier integrity and increases HIV access to target cells in the sub‐mucosa. In addition, innate responses to STIs can result in an increased number of immune cells, including those that are the primary targets of HIV, and may contribute to the association between STIs and increased susceptibility to HIV acquisition. Many of these cells are mediators of adaptive immunity, including tissue‐resident cells that may also display innate‐like functions. Bacterial vaginosis (BV) is another common cause of inflammation, and evidence for multiple interactions between BV, STIs and HIV suggest that susceptibility to these conditions should be considered in concert. Conclusions STIs and other microbes can induce inflammation in the genital tract, perturbing the normal robust function of the mucosal barrier against HIV. While the impact of STIs on the mucosal immune system and HIV acquisition is often under‐appreciated, understanding their interactions of the infections with the immune responses play an important role in improving treatment and reducing the risk of HIV acquisition. The frequent sub‐clinical inflammation associated with STIs underscores the need for better STI diagnostics to reverse the immunological consequences of infection.

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Section: Discussionsupporting

confidence: 63%

Mechanisms of sexually transmitted infection‐induced inflammation in women: implications for HIV risk

et al. 2019

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“…Interestingly, TLR9 has been found to play an important role after vaccination with the EV71 inactivated Ag as well as TLR4. TLR9 was reported to recognize DNA that contained sequences rich in CpG-DNA motifs like bacterial genomes[ 32 ] and viral DNA[ 33 ]. EV71 belongs to the Picornaviridae family using RNA as its genetic material[ 34 ], thus gDNA from host cell is regarded as the only source of DNA components in the EV71 vaccine.…”

Section: Discussionmentioning

confidence: 99%

Short-Fragment DNA Residue from Vaccine Purification Processes Promotes Immune Response to the New Inactivated EV71 Vaccine by Upregulating TLR9 mRNA

Shao¹,

Gao²,

Lin³

et al. 2016

PLoS ONE

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To reduce potential oncogenic long genomic DNA in vaccines, nuclease treatment has been applied in the purification processes. However, this action increased the residue of short-fragment DNA and its effect on vaccine potency was still elusive. In this study, we found residual sf-DNA in an inactivated EV71 vaccine could enhance humoral immune response in mice. Ag stimulation in vitro and vaccine injection in vivo revealed that TLR9 transcription level was elevated, indicating that sf-DNA could activate TLR9. These new findings will help us to understand the molecular mechanism induced by vero-cell culture-derived vaccines.

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“…TLR9 is overexpressed in cervical lesions, and is related to the histopathological grade and cervical cancer progression . HPV persistent infection without clearance increases TLR9 expression and TLR9 expression has been introduced as an applicable biomarker for malignant transformation of cervical squamous cells . It has been reported that some TLR9 polymorphisms, for example, rs187084 and rs352140, are associated with cervical cancer progression .…”

Section: Tlr9mentioning

confidence: 99%

Therapeutic potential of toll‐like receptors in treatment of gynecological cancers

et al. 2019

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Toll‐like receptors (TLRs) play an important role in the innate and adaptive immune system. They are expressed in various regions of the female reproductive tract, and their regulation may be involved in the pathogenesis of gynecological lesions. There is growing evidence that ligands for several TLRs are potentially anticancer agents, some of which have already been approved by the FDA, and these compounds are now undergoing clinical evaluation. There is a rationale for using these ligands as adjuvants in the treatment or prevention of gynecological cancer. Some TLR agonists that are of potential interest in the treatment of gynecological lesions include imiquimod, motolimod, cervarix, and CpG‐oligodeoxynucleotides (ODNs). In this review, we outline the different functions of TLRs in gynecological cancer with particular emphasis on the value of TLR agonists as a potential therapeutic target in the treatment of gynecological cancer. © 2019 IUBMB Life, 71(5):549–564, 2019

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TLR9 is expressed in human papillomavirus-positive cervical cells and is overexpressed in persistent infections

Cited by 40 publications

References 38 publications

Mechanisms of sexually transmitted infection‐induced inflammation in women: implications for HIV risk

Mechanisms of sexually transmitted infection‐induced inflammation in women: implications for HIV risk

Short-Fragment DNA Residue from Vaccine Purification Processes Promotes Immune Response to the New Inactivated EV71 Vaccine by Upregulating TLR9 mRNA

Therapeutic potential of toll‐like receptors in treatment of gynecological cancers

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