Results in immunology最新文献

Human Mycoplasma pneumoniae (MP) pneumonia is characterized by alveolar infiltration with neutrophils and lymphocytes and lymphocyte/plasma cell infiltrates in the peri-bronchovascular area (PBVA). No mouse model has been able to mimic the pathological features seen in human MP pneumonia, such as plasma cell-rich lymphocytic infiltration in PBVA. To figure out the mechanism for inflammation by MP infection using a novel mouse model that mimics human MP pneumonia, mice were pre-immunized intraperitoneally with Th2 stimulating adjuvant, alum, alone or MP extracts with an alum, followed by intratracheal challenge with MP extracts. The toll-like receptor-2, which is the major receptor for mycoplasma cell wall lipoproteins, was strongly up-regulated in alveolar macrophages in a latter group after the pre-immunization but prior to the intratracheal challenge. Those findings demonstrated that acceleration of innate immunity by antecedent antigenic stimulation can be an important positive-feedback mechanism in lung inflammation during MP pneumonia.

The transcription factor Ikaros family consists of five zinc-finger proteins: Ikaros, Aiolos, Helios, Eos and Pegasus; these proteins except Pegasus are essential for development and differentiation of lymphocytes. However, in B lymphocytes, the physiological role of Helios remains to be elucidated yet, because its expression level is very low. Here, we generated the Helios-deficient DT40 cells, Helios^−/−, and showed that the Helios-deficiency caused significant increases in transcriptions of four protein kinase Cs (PKCs); PKC-δ, PKC-ε, PKC-η and PKC-ζ, whereas their expressions were drastically down-regulated in the Aiolos-deficient DT40 cells, Aiolos^−/−. In addition, Helios^−/− was remarkably resistant against phorbol 12-myristate 13-acetate (PMA)/ionomycin treatment, which mimics the B cell receptor (BCR)-mediated stimulation. In the presence of PMA/ionomycin, their viability was remarkably higher than that of DT40, and their DNA fragmentation was less severe than that of DT40 in the opposite manner for the Aiolos-deficiency. The resistance against the PMA/ionomycin-induced apoptosis of Helios^−/− was sensitive to Rottlerin but not to Go6976. In addition, the Helios-deficiency caused remarkable up-regulation of the Rottlerin-sensitive superoxide (O₂⁻)-generating activity. These data suggest that Helios may contribute to the regulation of the BCR-mediated apoptosis and O₂⁻-generating activity, via transcriptional regulation of these four PKCs (especially PKC-δ) in immature B lymphocytes. Together with previous data, our findings may significantly help in the understanding of the B lymphocyte-specific expressions of PKC genes and molecular mechanisms of both the BCR-mediated apoptosis involved in negative selection and the O₂⁻-generating system in immature B lymphocytes.

There is a need for simple and physiological assays to characterize the immune status of allergic individuals. Whole blood samples from 15 adult subjects (10 with positive clinical history to grass pollen and 5 with negative clinical history) were obtained before the start (April 2010) and during the middle of the grass pollen season (June 2010). The investigators were blinded to the allergic status of the subjects. A skin prick test (SPT) to grass pollen was carried out at the end of the study. Cytokines (IL-5, IL-13, IL-10 and IFNγ) and activation of T-lymphocytes were determined after ex vivo culture of whole blood cells. IL-5, IL-10 and IL-13 cytokines were significantly elevated in allergic individuals during the middle of the season (p≤0.02) compared to the start. This assay can be a valuable tool in clinical trials especially in pediatric population where limited quantities of blood are available to study immune responses.

Natural killer cell enhancing factor (NKEF) belongs to the defined peroxiredoxin (Prx) family. Rock bream NKEF cDNA was identified by expressed sequence tag (EST) analysis of rock bream liver that was stimulated with the LPS. The full-length RbNKEF cDNA (1062 bp) contained an open reading frame (ORF) of 594 bp encoding 198 amino acids. RbNKEF was significantly expressed in the gill, liver, and intestine. mRNA expression of NKEF in the head kidney was examined under viral and bacterial challenge via real-time RT-PCR. Experimental challenge of rock bream with Edwardsiella tarda, Streptococcus iniae, and RSIV resulted in significant increases in RbNKEF mRNA in the head kidney. To obtain a recombinant NKEF, the RbNKEF ORF was expressed in Escherichia coli BL21 (DE3), and the purified soluble protein exhibited a single band corresponding to the predicted molecular mass. When kidney leucocytes were treated with a high concentration of rRbNKEF (10 μg/mL), they exhibited significantly enhanced cell proliferation and viability under oxidative stress.

Oxidative stress associated with nodavirus infection is poorly understood, especially pertaining to infection-mediated brain injury. Indirect evidence indicates that infection increases cellular abundance of reactive oxygen species (ROS) with consequent increase in cellular dityrosine production. The detection of dityrosine in nodavirus-infected grouper was demonstrated using immunohistochemical (IHC) staining. Proteomic analyses with eye tissues of healthy grouper revealed more abundant expression of crystallin protein in the eye than in various tissues, which was confirmed by real-time polymerase chain reaction and IHC analyses. Grouper crystallin belongs to a small heat shock protein family with chaperone-like function that prevents heat-induced and oxidative stress-induced protein aggregation. Recombinant crystallin induced nitric oxide (NO) production in RAW 264.7 cells after treatment. The results provide new insight into the pathogenesis of nodavirus and demonstrate an experimental rationale for antioxidant therapy research.