Plasmacytoid dendritic cells lead the charge against tumors

Jiménez-Baranda, Sonia; Silva, Inês Pires; Bhardwaj, Nina

doi:10.1172/jci61345

Cited by 2 publications

(2 citation statements)

References 24 publications

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“…pDCs express functional receptor for the anaphylatoxins C3a and C5a, and can also migrate in response to IL-18, an inflammasome-generated inflammatory mediator (Gutzmer et al 2006; Kaser et al 2004). Thus, in addition to chemotactic chemokines, pDCs can be recruited through signals associated with inflammation and tissue damage (Jimenez-Baranda et al 2012). We discuss below the crucial role of pDC recruitment at the site of HIV entry.…”

Section: 2 Plasmacytoid Dendritic Cell Biologymentioning

confidence: 99%

Plasmacytoid Dendritic Cells in HIV Infection

O’Brien

Manches

Bhardwaj

2012

Advances in Experimental Medicine and Biology

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Plasmacytoid dendritic cells (pDCs) are innate immune cells that are specialized to produce interferon-alpha (IFNα) and participate in activating adaptive immune responses. Although IFNα inhibits HIV-1 (HIV) replication in vitro, pDCs may act as inflammatory and immunosuppressive dendritic cells (DCs) rather than classical antigen-presenting cells during chronic HIV infection in vivo, contributing more to HIV pathogenesis than to protection. Improved understanding of HIV–pDC interactions may yield potential new avenues of discovery to prevent HIV transmission, to blunt chronic immune activation and exhaustion, and to enhance beneficial adaptive immune responses. In this chapter we discuss pDC biology, including pDC development from progenitors, trafficking and localization of pDCs in the body, and signaling pathways involved in pDC activation. We focus on the role of pDCs in HIV transmission, chronic disease progression and immune activation, and immu-nosuppression through regulatory T cell development. Lastly, we discuss potential future directions for the field which are needed to strengthen our current understanding of the role of pDCs in HIV transmission and pathogenesis.

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Section: 2 Plasmacytoid Dendritic Cell Biologymentioning

confidence: 99%

Plasmacytoid Dendritic Cells in HIV Infection

O’Brien

Manches

Bhardwaj

2012

Advances in Experimental Medicine and Biology

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“…Activation of TLRs by these pathogen-associated molecular patterns leads to induction of infection-fighting innate immune responses (1). Various TLR agonists have been considered for multiple clinical applications, including cancer immunotherapy (2)(3)(4), and one, the TLR7 agonist imiquimod, is approved for topical treatment of basal cell carcinoma (5).…”

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confidence: 99%

Central role of liver in anticancer and radioprotective activities of Toll-like receptor 5 agonist

Burdelya

Brackett

Kojouharov

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

111

175

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Vertebrate Toll-like receptor 5 (TLR5) recognizes bacterial flagellin proteins and activates innate immune responses to motile bacteria. In addition, activation of TLR5 signaling can inhibit growth of TLR5-expressing tumors and protect normal tissues from radiation and ischemia-reperfusion injuries. To understand the mechanisms behind these phenomena at the organismal level, we assessed nuclear factor kappa B (NF-κB) activation (indicative of TLR5 signaling) in tissues and cells of mice treated with CBLB502, a pharmacologically optimized flagellin derivative. This identified the liver and gastrointestinal tract as primary CBLB502 target organs. In particular, liver hepatocytes were the main cell type directly and specifically responding to systemic administration of CBLB502 but not to that of the TLR4 agonist LPS. To assess CBLB502 impact on other pathways, we created multireporter mice with hepatocytes transduced in vivo with reporters for 46 inducible transcription factor families and found that along with NF-κB, CBLB502 strongly activated STAT3-, phenobarbital-responsive enhancer module (PREM), and activator protein 1 (AP-1-) -driven pathways. Livers of CBLB502-treated mice displayed induction of numerous immunomodulatory factors and massive recruitment of various types of immune cells. This led to inhibition of growth of liver metastases of multiple tumors regardless of their TLR5 status. The changed liver microenvironment was not, however, hepatotoxic, because CBLB502 induced resistance to Fas-mediated apoptosis in normal liver cells. Temporary occlusion of liver blood circulation prevented CBLB502 from protecting hematopoietic progenitors in lethally irradiated mice, indicating involvement of a factor secreted by responding liver cells. These results define the liver as the key mediator of TLR5-dependent effects in vivo and suggest clinical applications for TLR5 agonists as hepatoprotective and antimetastatic agents.breast cancer | colon cancer | neutrophils | natural killer cells | Salmonella T oll-like receptors (TLRs) recognize and are activated by specific patterns in molecules that are produced by a broad range of microbial pathogens but are not present in host molecules. Activation of TLRs by these pathogen-associated molecular patterns leads to induction of infection-fighting innate immune responses (1). Various TLR agonists have been considered for multiple clinical applications, including cancer immunotherapy (2-4), and one, the TLR7 agonist imiquimod, is approved for topical treatment of basal cell carcinoma (5).Although signaling pathways induced by different TLRs all result in mobilization of an innate immune response and involve activation of nuclear factor kappa B (NF-κB), the key regulator of immunity (6, 7), TLR5 is a particularly attractive candidate for therapeutic targeting for several reasons. First, bacterial flagellin, the natural ligand of TLR5, was found to have strong radioprotective effects in rodents and nonhuman primates (8). CBLB502 is a rationally designed derivative of Salmon...

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Plasmacytoid dendritic cells lead the charge against tumors

Cited by 2 publications

References 24 publications

Plasmacytoid Dendritic Cells in HIV Infection

Plasmacytoid Dendritic Cells in HIV Infection

Central role of liver in anticancer and radioprotective activities of Toll-like receptor 5 agonist

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