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Monocytes represent a class of immune cells that play a key role in the innate and adaptive immune response against infections. One mechanism employed by monocytes for sensing foreign antigens is via toll-like receptors (TLRs)--transmembrane proteins that distinguish classes of foreign pathogens, for example, bacteria (TLR4, 5, and 9) vs. fungi (TLR2) vs. viruses (TLR3, 7, and 8). Binding of antigens activates a signaling cascade through TLR receptors that culminate in secretion of inflammatory cytokines. Detection of these cytokines can provide valuable clinical data for drug developers and disease investigations, but this usually requires a large sample volume and can be technically inefficient with traditional techniques such as flow cytometry, enzyme-linked immunosorbent assay, or luminex. This paper describes an approach whereby antibody arrays for capturing cells and secreted cytokines are encapsulated within a microfluidic device that can be reconfigured to operate in serial or parallel mode. In serial mode, the device represents one long channel that may be perfused with a small volume of minimally processed blood. Once monocytes are captured onto antibody spots imprinted into the floor of the device, the straight channel is reconfigured to form nine individually perfusable chambers. To prove this concept, the microfluidic platform was used to capture monocytes from minimally processed human blood in serial mode and then to stimulate monocytes with different TLR agonists in parallel mode. Three cytokines, tumor necrosis factor-a, interleukin (IL)-6, and IL-10, were detected using anti-cytokine antibody arrays integrated into each of the six chambers. We foresee further use of this device in applications such as pediatric immunology or drug/vaccine testing where it is important to balance small sample volume with the need for high information content. [ABSTRACT FROM AUTHOR]

The ideal cancer therapy not only induces the death of all localized tumor cells without damage to surrounding normal tissue, but also activates a systemic antitumor immunity. High intensity focused ultrasound (HIFU) has the potential to be such a treatment, as it can non-invasively ablate a targeted tumor below the skin surface, and may subsequently augment host antitumor immunity. This paper is to review increasing pre-clinical and clinical evidence linking antitumor immune response to HIFU ablation, and to discuss the potential mechanisms involved in HIFU-enhanced host antitumor immunity. The seminal studies performed so far indicate that although it is not possible to conclude definitively on the connection between HIFU treatment and antitumor immune response, it is nonetheless important to conduct extensive studies on the subject in order to elucidate the processes involved. [ABSTRACT FROM AUTHOR]

Cytokine storm is characterized by increased levels of proinflammatory cytokines. Magnetic nanoparticles (MNPs)-conjugated antibody therapy is promising in treating cytokine storms. This study will evaluate the time-dependent distribution of the silica-coated MNP (MNP-Si) in the spleen and consequent serum cytokine changes for 30 days. MNP-Si were administered to female BALB/c mice via the tail vein injection. The distribution of Fe in the spleen tissue was analyzed by ICP-MS both in control and MNP-Si-treated mice. Moreover, the acute immune toxicity in serum was investigated by analyzing IFN-γ and IL-6 levels. Fe in the control spleen is 0.98 × 106μg/mg of dry weight. The highest average concentration of Fe in the spleen was measured on day 10 (1.4 × 106μg/mg). And at day 30, Fe levels decreased to 1.0 × 106μg/mg. IFN-γ levels significantly increase to a maximum on day 6 and remain elevated until day 30. IL-6 levels are not elevated after MNP-Si administration. Although the cytokines in tissue homogenates were elevated at day 20, the data are statistically non-significant. In conclusion, the proinflammatory cytokine IFN-γ levels were increased on day 6, indicating induced activation of macrophages and systemic inflammation after MNP-Si administration. Therefore, the dose and composition of the MNP-Si should be revised for potential usage for therapeutic purposes. [ABSTRACT FROM AUTHOR]

Platelets are considered to have important functions in inflammatory processes as key players in innate immunity. Toll like receptors (TLRs), expressed on platelets, recognize pathogen associated molecular patterns and trigger immune responses. Pathogens are able to adhere to human tissues and form biofilms which cause a continuous activation of the immune system. The authors aimed to investigate how immobilized Pam3CSK4 (a synthetic TLR2/1 agonist) and IgG, respectively, resembling a bacterial focus, affects adhesion and activation of platelets including release of two cytokines, regulated on activation normal T-cell expressed and secreted (RANTES) and macrophage migration inhibitory factor (MIF). The authors also aim to clarify the signaling downstream of TLR2/1 and FccRII (IgG receptor) and the role of adenine nucleotides in this process. Biolayers of Pam3CSK4 and IgG, respectively, were confirmed by null-ellipsometry and contact angle measurements. Platelets were preincubated with signaling inhibitors for scr and Syk and antagonists for P2X1 or P2Y1 [adenosine triphosphate (ATP), adenosine diphosphate (ADP) receptors] prior to addition to the surfaces. The authors show that platelets adhere and spread on both Pam3CSK4- and IgG-coated surfaces and that this process is antagonized by scr and Syc inhibitors as well as P2X1 and P2Y antagonists. This suggests that Pam3CSK4 activated platelets utilize the same pathway as FcγRII. Moreover, the authors show that ATP-ligation of P2X1 is of importance for further platelet activation after TLR2/1-activation, and that P2Y12 is the prominent ADP-receptor involved in adhesion and spreading. RANTES and MIF were secreted over time from platelets adhering to the coated surfaces, but no MIF was released upon stimulation with soluble Pam3CSK4. These results clarify the importance of TLR2/1 and FcγRII in platelet adhesion and activation, and strengthen the role of platelets as an active player in sensing bacterial infections. [ABSTRACT FROM AUTHOR]