Significance of Toll-like Receptors Expression in Tumor Growth and Spreading: A Short Review

Toll-like receptors (TLRs) are considered now as crucial sensors of innate immunity. Their role in the recognition of pathogens and the initiation of adaptive immune responses against them is well known. However, in last years TLRs have been identified on several tumor cells, including human malignancies. Their expression in cancer was found to be twofold: either promoting or inhibiting tumor progression. It was also demonstrated that several TLRs agonists, either natural or synthetic ones, may have beneficial effect on tumor-mediated disease, leading to potentiation of immune response to tumor-associated antigens. TLR-agonist linked tumor immunotherapy is still in nascent state, but growing rapidly, also in the area of common human malignancies. To date, the most promising and the most frequently studied interaction in tumor immunotherapy trials seems to be TLR9 and its synthetic agonists

TLR4 signalling in pulmonary stromal cells is critical for inflammation and immunity in the airways

Inflammation of the airways, which is often associated with life-threatening infection by Gram-negative bacteria or presence of endotoxin in the bioaerosol, is still a major cause of severe airway diseases. Moreover, inhaled endotoxin may play an important role in the development and progression of airway inflammation in asthma. Pathologic changes induced by endotoxin inhalation include bronchospasm, airflow obstruction, recruitment of inflammatory cells, injury of the alveolar epithelium, and disruption of pulmonary capillary integrity leading to protein rich fluid leak in the alveolar space. Mammalian Toll-like receptors (TLRs) are important signalling receptors in innate host defense. Among these receptors, TLR4 plays a critical role in the response to endotoxin

Decreased Pre-existing Ad5 Capsid and Ad35 Neutralizing Antibodies Increase HIV-1 Infection Risk in the Step Trial Independent of Vaccination

<div><h3>Background</h3><p>The Step trial raised the possibility that uncircumcised men with pre-existing Ad5 neutralizing antibodies carried an increased risk of HIV infection after vaccination. Thus, understanding Ad seropositivity in humans is important to the development of an AIDS vaccine. Here, we analyze the impact of different Ad5-specific neutralizing antibodies on immune function and clinical outcome.</p> <h3>Methods and Findings</h3><p>Ad seropositivity in the Step trial volunteers was analyzed using chimeric rAd5/35 vectors to characterize their specificity for Ad5 fiber and non-fiber external (capsid) proteins. Immune responses and HIV seropositivity were correlated with the specificity of Ad5-neutralizing antibodies. Neutralizing antibodies induced by the vaccine in Ad5 seronegative subjects were directed preferentially to Ad5 capsid proteins, although some fiber-neutralizing antibodies could be detected. Pre-vaccination Ad5 serostatus did not affect the capsid-directed response after three vaccinations. In contrast, anti-fiber antibody titers were significantly higher in volunteers who were Ad5 seropositive prior to vaccination. Those Ad5 seropositive subjects who generated anti-capsid responses showed a marked reduction in vaccine-induced CD8 responses. Unexpectedly, anti-vector immunity differed qualitatively in Ad5 seropositive participants who became HIV-1 infected compared to uninfected case controls; Ad5 seropositive participants who later acquired HIV had lower neutralizing antibodies to capsid. Moreover, Ad35 seropositivity was decreased in HIV-infected subjects compared with uninfected case controls, while seroprevalence for other serotypes including Ad14, Ad28 and Ad41 was similar in both groups.</p> <h3>Conclusions</h3><p>Together, these findings suggest that the case subjects were less immunologically responsive prior to infection. Subjects infected during the Step trial had qualitative differences in immunity that increased their risk of HIV-1 infection independent of vaccination.</p> </div

Positive control of colanic acid synthesis in Escherichia coli by rmpA and rmpB, two virulence-plasmid genes of Klebsiella pneumoniae

In Klebsiella pneumoniae, the mucoid phenotype, which is a virulence factor, is distinct from capsule production. It is positively controlled by a plasmid gene, designated rmpA. When introduced into certain Escherichia coli strains, rmpA induces expression of a mucoid phenotype, which results from overproduction of colanic acid at 30 degrees C but not at 37 degrees C. In E. coli, production of colanic acid is regulated by three genes: rcsA and rcsB which act as positive regulators, and rcsC which is a negative effector. In this work we present evidence that the rmpA gene complemented an rcsA, Ion double mutant of E. coli, but not an rcsA, Ion+ isolate. This leads to the suggestion that rmpA expressed an rcsA-like activity and like rcsA, was negatively controlled at post-transcriptional level by the Lon protease. The nucleotide sequence of rmpA is reported. No homology could be found between the 27 kiloDalton RcsA protein and the deduced amino acid sequence of the 15.5 kiloDalton RmpA protein. Another gene, rmpB, which was required in E. coli recA isolates for full expression of rmpA at 30 degrees C, has been identified on the K. pneumoniae virulence plasmid and shown to encode a 37 kiloDalton protein. Although rmpB was closely linked to rmpA, it was not present on the same transcriptional unit. These results suggested that induction of colanic acid synthesis by the K. pneumoniae virulence gene rmpA, was, at least in E. coli, under the control of the RecA network via rmpB, which may act as a positive regulator of rmpA. We conclude that these plasmid genes may function in K. pneumoniae as regulatory genes controlling the mucoid phenotype, which is itself encoded by the chromosome

Acoustically Induced Spin Resonances of Silicon-Vacancy Centers in <math display="inline" overflow="scroll"><mn>4</mn><mi>H</mi></math>-SiC

International audienceThe long-lived and optically addressable spin states of silicon vacancies (VSi) in 4H-SiC make them promising qubits for quantum communication and sensing. These color centers can be created in both the hexagonal (V1) and in the cubic (V2) local crystallographic environments of the 4H-SiC host. While the spin of the V2 center can be efficiently manipulated by optically detected magnetic resonance at room temperature, spin control of the V1 center above cryogenic temperatures has so far remained elusive. Here, we show that the dynamic strain of surface acoustic waves can overcome this limitation and efficiently excite magnetic resonances of V1 centers up to room temperature. Based on the width and temperature dependence of the acoustically induced spin resonances of the V1 centers, we attribute them to transitions between spin sublevels in the excited state. The acoustic spin control of both kinds of VSi centers in their excited states opens alternative ways for applications in quantum technologies based on spin optomechanics

Identification of acoustically induced spin resonances of Si vacancy centers in 4H-SiC

Silicon vacancies ($\mathrm{V_{Si}}$) in the 4H polytype of SiC form color centers with long-lived and optically addressable spin states, which make them promising spin qubits for quantum communication and sensing. These centers can be created both in the cubic ($V2$) and in the hexagonal ($V1$) local crystallographic environments of the 4H-SiC host. While the $V2$ center can be efficiently manipulated by optically detected magnetic resonance (ODMR) even at room temperature, ODMR control of the $V1$ centers could so far only been achieved at cryogenic temperatures. Here, we show that magnetic resonance induced by the dynamic strain of a surface acoustic wave can overcome this limitation and enable the efficient manipulation of $V1$ centers up to room temperatures. Based on the width and temperature dependence of the acoustically induced spin resonances, we attribute them to spin transitions between the $+3/2$ and $-1/2$ spin sublevels of the excited state of the $V1$ centers. These results are an important step towards on-chip quantum information processing based on $\mathrm{V_{Si}}$ centers driven by acoustic fields