instruction:
In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
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Dendritic cells (DCs) are recognized as highly potent antigen-presenting cells that are able to stimulate cytotoxic T lymphocyte (CTL) responses with antitumor activity. Consequently, DCs have been explored as cellular vaccines in cancer immunotherapy. To that end, DCs are modified with tumor antigens to enable presentation of antigen-derived peptides to CTLs. In this review we discuss the use of viral vectors for in situ modification of DCs, focusing on their clinical applications as anticancer vaccines. Among the viral vectors discussed are those derived from viruses belonging to the families of the Poxviridae, Adenoviridae, Retroviridae, Togaviridae, Paramyxoviridae, and Rhabdoviridae. We will further shed light on how the combination of viral vector-based vaccination with T-cell supporting strategies will bring this strategy to the next level. Since their discovery in 1973, it was clear that dendritic cells (DCs) stood out above the immune cell pack (1, 2). They are morphologically distinct from all other immune cell types and are gifted with an unparalleled capacity to take up, process and present self and foreign antigens to both CD4 + and CD8 + T cells. DCs are critical intermediaries between the innate and adaptive immune systems, as they stimulate, regulate, and shape both immunity and tolerance in all its disguises. Ralph Steinmann, who discovered these cells, was awarded the Nobel Prize for Medicine in 2011, because the discovery of DCs changed medicine (3). Dendritic cells in both humans and mice represent a population of at least four different subtypes with distinct phenotypical and functional characteristics (4-7). These subsets are: plasmacytoid DCs (pDCs), two subsets of conventional DCs (cDC1 and cDC2), and inflammatory DCs. The latter represent a monocyte-derived subset that appears during inflammatory responses (Table 1) . Recently, additional types of human blood DCs, monocytes, and progenitors were revealed using single cell RNA-sequencing. The group of Prof. Nir Hacohen identified pDCs next to cDC progenitor-derived cDC1 (Clec9A + ) and two types of CD1c + cDC2, of which one can also be derived from CD14 + DCs. Furthermore they found a CD141 − CD1c − CD11c + DC subset derived from CD16 + monocytes and an AXL + Siglec6 + subset (8). Future research will have to unravel a possible murine representative for the human cDC2 and AXL + Siglec6 + DC subset. Also, Langerhans cells have been considered an important DC subset for vaccination as they are localized in the epidermis (HLA-DR + CD11c + CD1a + CD207 + ). However, recent evidence suggests that they are related to macrophages, another antigen-presenting cell (APC) type with potential antitumor activity (9).
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The Journey of in vivo Virus Engineered Dendritic Cells From Bench to Bedside: A Bumpy Road


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Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV) and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H + -ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.
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Niclosamide Is a Proton Carrier and Targets Acidic Endosomes with Broad Antiviral Effects


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Please cite this article in press as: Roodgar, M., et al. Inducible nitric oxide synthase (iNOS) regulatory region variation in non-human primates. Infect. Genet. Evol. (2015), http://dx.(Chlorocebus sabaeus), pig-tailed macaques (Macaca nemestrina), 81 cynomolgus macaques (Macaca fascicularis), Indian rhesus 82 macaques (M. mulatta), and Chinese rhesus macaques (M. mulatta). Variation in regulation of iNOS expression may play a role in the var-84 iable susceptibility of these species to several infectious diseases 85 (Roodgar et al., 2013; Lyashchenko et al., 2007; McAuliffe et al., 86 2004). We investigated whether or not there is evidence for inter-87 species differences in the regulatory regions of iNOS that might 88 account for such variability in disease susceptibility. Since NOS2A 89 plays a key role in immunity against intracellular pathogens 90 (Wienerroither et al., 2014; Obermajer et al., 2013) relevant to 91 human health, information on DNA sequence variation in the regu-92 latory region of NOS2A in species of NHP that are more closely 93 related to humans than the mouse should provide better informa-94 tion about the relationship between variation in NOS2A gene expres-95 sion and human-like immune responses to intracellular pathogens 96 (Lyashchenko et al., 2007; McAuliffe et al., 2004). 97 We sequenced two candidate regulatory regions of the NOS2A 98 gene in several animals in each of five species or subspecies of 99 NHP that exhibit differing levels of susceptibility to infectious 100 respiratory diseases, especially tuberculosis. The basic primer 101 sequences for the candidate iNOS promoter regions were identified 102 using the human genome Chip-seq data available at the University 103 of California, Santa Cruz (UCSC) Genome Browser. We then used an 104 Applied Biosystems 3130XL genetic analyzer to produce DNA 105 sequence data for each sample. Sequences were aligned using 106 Kalign2 (Lassmann et al., 2009; Lassmann and Sonnhammer, 107 2006; Lassmann and Sonnhammer, 2005), and variation in the can-108 didate promoter regions was analyzed using the adegenet package 109 in the R programming environment (R Core Team, 2014). The effect 110 of cross-species genetic conservation and variation on transcrip-111 tion factor and regulatory element bindings sites was then 112 evaluated using the MatInspector software (Quandt et al., 1995; 113 Cartharius et al., 2005). 114 2. Results 115 2.1. Multiple sequence alignment and promoter localization 116 We localized the iNOS coding region and the candidate pro-117 moter/regulatory regions on the rhesus macaque and human refer-118 ence sequences using the NCBI genome browser. Fig. 1 plots the 119 location of the R2 region on the human reference sequence. 120 Multiple sequence alignment of R1 and R2 across species was 121 conducted using Kalign2 (Lassmann et al., 2009; Lassmann and 122 Sonnhammer, 2006; Lassmann and Sonnhammer, 2005). The 123 performance of the alignment was evaluated using Mumsa 124 (Lassmann and Sonnhammer, 2006) and visual inspection. The 125 Jalview program (Clamp et al., 2004; Waterhouse et al., 2009) 126 was used to visualize and trim the alignments and construct spe-127 cies-specific consensus sequences. In Fig. 2, we plot the animal-128 specific nucleotide sequences and species-specific consensus 129 sequences used in this analysis. 130 2.2. Promoter variation and interspecies clustering 131 To investigate whether or not variation in R1 and R2 followed 132 the pattern expected from the phylogenetic relationships among 133 these NHP species and subspecies, we used the R packages ape 134 and adegent to extract the SNPs from the aligned and trimmed 135 DNA sequences. We then used discriminant analysis of principal 136 components (DAPC) (Jombart et al., 2010) to investigate the 137 cross-species partitioning of genetic variation. 138
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Inducible nitric oxide synthase (iNOS) regulatory region variation in 4 non-human primates 5 6 7