This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ http://www.biomedcentral.com/bmcimmunol/mostviewed/ Most viewed articles in last 30 days from BMC Immunology (ISSN 1471-2172) published by BioMed Central Background: Streptococcus pneumoniae is a human pathogenic bacteria and a major cause of severe invasive diseases, including pneumonia, bacteremia, and meningitis. Infections with S. pneumoniae evoke a strong inflammatory response, which plays a major role in the pathogenesis of pneumococcal disease. Results: In this study, we have examined how S. pneumoniae affects expression of the inflammatory cytokine tumor necrosis factor (TNF) α, and the molecular mechanisms involved. Secretion of TNF-α was strongly induced by S. pneumoniae, which was able to stabilize TNF-α mRNA through a mechanism dependent on the viability of the bacteria as well as the adenylate uridylate-rich elements in the 3'untranslated region of TNF-α mRNA. The ability of S. pneumoniae to stabilize TNF-α mRNA was dependent on the mitogen-activated protein kinase (MAPK) p38 whereas inhibition of Toll-like receptor signaling via MyD88 did not affect S. pneumoniae-induced mRNA stabilization. P38 was activated through a pathway involving the upstream kinase transforming growth factor-activated kinase 1 and MAPK kinase 3. Conclusion: Thus, S. pneumoniae stabilizes TNF-α mRNA through a pathway dependent on p38 but independent of Toll-like receptors. Production of TNF-α may contribute significantly to the inflammatory response raised during pneumococcal infection. http://www.biomedcentral.com/1471-2172/9/52 Trine H Mogensen, Randi S Berg, Lars Østergaard and Søren R Paludan BMC Immunology 2008, 9:52 Number of accesses: 500 2008-09-16 doi:10.1186/1471-2172-9-52 BMC Immunology 1471-2172 9 52 2008-09-16 Background: Type I diabetes (TID) is an autoimmune disease resulting from destruction of the insulin-producing β-cells by autoreactive T cells. Studies have shown that polymorphisms of chemokine CXCL12 gene are linked to TID in humans. In non-obese diabetic (NOD) mice, which are predisposed to develop the disease, reduction of CXCL12 level leads to significant delays in the onset of diabetes. Despite these initial observations, however, how CXCL12 affects development of TID has not been fully investigated. Results: We found that the level of CXCL12 transcript is significantly elevated in the bone marrow of NOD mice as compared to Balb/c and C57BL/6 mice. Correspondingly, naïve T cells, regulatory T cells and hematopoietic stem cells (HSC) accumulate in the bone marrow of NOD mice. Treatment of NOD mice with AMD3100, an antagonist for CXCL12's receptor CXCR4, mobilizes T cells and HSC from the bone marrow to the periphery, concomitantly inhibits insulitis and delays the onset of diabetes. Conclusion: These results suggest that the elevated CXCL12 expression promotes TID in NOD mice by altering T cell and hematopoietic stem cell trafficking. The findings highlight the potential usefulness of AMD3100 to treat or prevent TID in humans. http://www.biomedcentral.com/1471-2172/9/51 Qibin Leng, Yuchun Nie, Yongrui Zou and Jianzhu Chen BMC Immunology 2008, 9:51 Number of accesses: 422 2008-09-15 doi:10.1186/1471-2172-9-51 BMC Immunology 1471-2172 9 51 2008-09-15 Background: Dendritic cells (DCs) are antigen presenting cells capable of inducing innate and adaptive immune responses. According to the stimulus and their maturation state, DCs induce immunogenic or tolerogenic responses. Platelets (PLTs), which are involved in haemostasis and inflammation, can also interact with DCs. In this study, we examined the effect of PLTs on DC maturation in vitro. Human monocyte-derived DCs were co-cultured for 2 days with homologous PLTs either in the same well or in 0.4 μm-pore size filter-separated compartments. Results: Confocal microscopy showed the attachment of PLTs to DC membranes. The DC receptor involved in this interactions was found to be CD162. In addition, we observed that DCs co-cultured with PLTs in filter-separated compartments acquired a mature phenotype (high CD80, CD86, and intermediate CD83 expression; IL-12(p70) production; efficient stimulation of autologous CD4+ T cell proliferation), while DCs co-cultured with PLTs in the same compartment did not undergo phenotypic maturation, did not secrete IL-12(p70) or IL-1β, but instead induced moderate Th2-polarized T cell proliferation. Conclusion: These data indicate that (i) PLTs secrete a soluble DC-activating factor that was demonstrated not to be soluble CD40-Ligand (CD154; as could have been expected from in vivo and previous in vitro work) but to be nucleotide, and (ii) that cell-to-cell contact did not induce DC maturation, possibly because nucleotide release by PLTs was prevented by direct contact with DCs. This work demonstrates that PLTs are active elements of the immune system that might play a role in balancing the ability of DCs to polarize T cell responses, therefore making them critical factors in transfusion processes. http://www.biomedcentral.com/1471-2172/9/54 Hind Hamzeh-Cognasse, Fabrice Cognasse, Sabine Palle, Patricia Chavarin, Thomas Olivier, Olivier Delézay, Bruno Pozzetto and Olivier Garraud BMC Immunology 2008, 9:54 Number of accesses: 406 2008-09-25 doi:10.1186/1471-2172-9-54 BMC Immunology 1471-2172 9 54 2008-09-25 Background: CD8+ regulatory T cells (Treg) have been considered to be involved in a model of ocular-induced tolerance, known as anterior chamber-associated immune deviation (ACAID). The phenotype and characteristics of CD8+Treg in ACAID remain only poorly understood. Recent studies have reported that the CD94-Qa-1 system is implicated in the induction of ACAID CD8+Treg, but the functions and characteristics of CD8+CD94+T cells remain unclear. Results: Both mRNA and protein of CD94 and NKG2A were markedly up-regulated on splenic CD8+T cells of ACAID mice compared with controls. Flow cytometric analysis showed that very few CD8+CD94+T cells express granzyme B, perforin and Foxp3. CD8+CD94+T cells, but not CD8+CD94-T cells, magnetically isolated from the spleens of ACAID mice, produced large amounts of TGF-beta1 and exhibited suppressive activity in vitro. Neutralization of TGF-beta1 caused reversal of suppression mediated by CD8+CD94+T cells. Conclusion: CD8+CD94+T cells from ACAID mice exhibited suppressive activity in association with enhanced expression of TGF-beta1, suggesting that CD8+Treg are mainly distributed in CD94+T cell subpopulations. http://www.biomedcentral.com/1471-2172/9/53 Hao He, Peizeng Yang, Liqiong Jiang, Junfeng Zhang, Changlin Zhao, Lina Chen, Xiaomin Lin, Hongyan Zhou and Aize Kijlstra BMC Immunology 2008, 9:53 Number of accesses: 337 2008-09-25 doi:10.1186/1471-2172-9-53 BMC Immunology 1471-2172 9 53 2008-09-25 Background: Amplification and cloning of naïve T cell Receptor (TR) repertoires or antigen-specific TR is crucial to shape immune response and to develop immuno-based therapies. TR variable (V) regions are encoded by several genes that recombine during T cell development. The cloning of expressed genes as large diverse libraries from natural sources relies upon the availability of primers able to amplify as many V genes as possible. Results: Here, we present a list of primers computationally designed on all functional TR V and J genes listed in the IMGT®, the ImMunoGeneTics information system®. The list consists of unambiguous or degenerate primers suitable to theoretically amplify and clone the entire TR repertoire. We show that it is possible to selectively amplify and clone expressed TR V genes in one single RT-PCR step and from as little as 1000 cells. Conclusion: This new primer set will facilitate the creation of more diverse TR libraries than has been possible using currently available primer sets. http://www.biomedcentral.com/1471-2172/9/50 Ilenia Boria, Diego Cotella, Irma Dianzani, Claudio Santoro and Daniele Sblattero BMC Immunology 2008, 9:50 Number of accesses: 324 2008-08-29 doi:10.1186/1471-2172-9-50 BMC Immunology 1471-2172 9 50 2008-08-29 Background: Cytokine-stimulated endothelial cells (EC) propagate hematopoietic progenitor cell (HPC) expansion. However, the effects on the functional capacities of cultured progenitors have not been evaluated. HPC were assessed by flow cytometry, colony and cobblestone assays and long-term cultures (LTC) after culturing in the supernatant of EC stimulated by IL-1beta, IL-3 or IL-6. Results: EC incubation with IL-6 did not improve cell expansion in comparison to non-stimulated EC supernatant, while the HPCs' phenotype and functional capacities were retained. In contrast, IL-1beta and IL-3 stimulation resulted in a 10- and 100-fold increase in cell numbers with more than 90% of these cells being CD33(+). Plating efficiencies and LTC initiating cells were greatest in IL-6 supernatants, whereas the highest numbers of burst-forming units were observed using IL-3. IL-1beta supernatants diminished the number of 5-week cobblestone-areas, whereas the number of 2-week cobblestone areas remained equal to freshly isolated HPC. Fewer 2-week cobblestones and greater amounts of 5-week cobblestones were observed with IL-6 and IL-3. Expanded progenitors from all interleukin conditions were further matured into functional granulocytes. Conclusion: IL-1beta and IL-3 stimulated endothelium induces proliferation and differentiation of myeloid precursors, while IL-6 treatment induced a benefit of HPC survival. http://www.biomedcentral.com/1471-2172/9/56 Anja Moldenhauer, Gesche Genter, Andreas Lun, Gurkan Bal, Holger Kiesewetter and Abdulgabar Salama BMC Immunology 2008, 9:56 Number of accesses: 312 2008-10-01 doi:10.1186/1471-2172-9-56 BMC Immunology 1471-2172 9 56 2008-10-01 Background: We performed initial cell, cytokine and complement depletion studies to investigate the possible role of these effectors in response to vaccination with heat-killed Burkholderia mallei in a susceptible BALB/c mouse model of infection. Results: While protection with heat-killed bacilli did not result in sterilizing immunity, limited protection was afforded against an otherwise lethal infection and provided insight into potential host protective mechanisms. Our results demonstrated that mice depleted of either B cells, TNF-α or IFN-γ exhibited decreased survival rates, indicating a role for these effectors in obtaining partial protection from a lethal challenge by the intraperitoneal route. Additionally, complement depletion had no effect on immunoglobulin production when compared to non-complement depleted controls infected intranasally. Conclusion: The data provide a basis for future studies of protection via vaccination using either subunit or whole-organism vaccine preparations from lethal infection in the experimental BALB/c mouse model. The results of this study demonstrate participation of B220+ cells and pro-inflammatory cytokines IFN-γ and TNF-α in protection following HK vaccination. http://www.biomedcentral.com/1471-2172/9/55 Gregory C Whitlock, Roman A Lukaszewski, Barbara M Judy, Slobodan Paessler, Alfredo G Torres and D Mark Estes BMC Immunology 2008, 9:55 Number of accesses: 303 2008-09-29 doi:10.1186/1471-2172-9-55 BMC Immunology 1471-2172 9 55 2008-09-29 Background: Human mast cell (HuMC) maturation occurs in tissues interfacing with the external environment, exposing both mast cell progenitors and mature mast cells, to bacteria and their products. It is unknown, however, whether long- or short-term exposure to bacteria-derived toll-like receptor (TLR) ligands, such as lipopolysaccharide (LPS) or peptidoglycan (PGN), influences HuMC biology. Results: Over 6 wks of culture, LPS had minimal effect on HuMC numbers but increased CD117, tryptase and chymase expression. PGN inhibited HuMC development. For mature mast cells, LPS in the presence of rhSCF (10 ng/ml) increased CD117, tryptase, chymase and carboxypeptidase expression, primarily in CD117low HuMC. LPS decreased FcεRI expression and β-hexosaminidase release; but had no effect on LTC4 and PGD2 production. PGN reduced HuMC numbers; and CD117 and tryptase expression. IL-1β and IL-6 (in addition to IL-8 and IL-12) were detected in short-term culture supernatants of LPS treated cells, and reproduced the increases in CD117, tryptase, chymase, and carboxypeptidase expression observed in the presence of LPS. Comparative studies with mouse bone marrow-derived mast cells from wild type, but not TLR4 knockout mice, showed increases in mRNA of mouse mast cell chymases MMCP-1, MMCP-2 and MMCP-4. Conclusion: PGN inhibits HuMC growth, while LPS exerts its primary effects on mature HuMC by altering cytokine production and protease composition, particularly at low concentrations of SCF. These data demonstrate the ability of bacterial products to alter HuMC mediator production, granular content, and number which may be particularly relevant at mucosal sites where HuMC are exposed to these products. http://www.biomedcentral.com/1471-2172/9/45 Arnold S Kirshenbaum, Emily Swindle, Marianna Kulka, Yalin Wu and Dean D Metcalfe BMC Immunology 2008, 9:45 Number of accesses: 298 2008-08-07 doi:10.1186/1471-2172-9-45 BMC Immunology 1471-2172 9 45 2008-08-07 Background: The USDA, Wildlife Services cooperative oral rabies vaccination (ORV) program uses a live vaccinia virus-vectored (genus Orthopoxvirus) vaccine, Raboral V-RG(R) (V-RG), to vaccinate specific wildlife species against rabies virus in several regions of the U.S. Several naturally occurring orthopoxviruses have been found in North America, including one isolated from asymptomatic raccoons (Procyon lotor). The effect of naturally occurring antibodies to orthopoxviruses on successful V-RG vaccination in raccoons is the focus of this study. Results: Overall, raccoons pre-immunized (n = 10) with a recombinant raccoonpox virus vaccine (RCN-F1) responded to vaccination with V-RG with lower rabies virus neutralizing antibody (VNA) titers than those which were not pre-immunized (n = 10) and some failed to seroconvert for rabies VNA to detectable levels. Conclusions: These results suggest that the success of some ORV campaigns may be hindered where raccoonpox virus or possibly other orthopoxvirus antibodies are common in wildlife species targeted for ORV. If these areas are identified, different vaccination strategies may be warranted. http://www.biomedcentral.com/1471-2172/9/57 J. JEFFREY Root, Robert G McLean, Dennis Slate, Kathleen A MacCarthy and Jorge E Osorio BMC Immunology 2008, 9:57 Number of accesses: 277 2008-10-03 doi:10.1186/1471-2172-9-57 BMC Immunology 1471-2172 9 57 2008-10-03 Background: Melioidosis, a lethal tropical infection that is endemic in southeast Asia and northern Australia, is caused by the saprophytic Gram-negative bacterium Burkholderia pseudomallei. Overall mortality approaches 40% yet little is known about mechanisms of host defense. Toll-like receptors (TLRs) are host transmembrane receptors that recognize conserved pathogen molecular patterns and induce an inflammatory response. The lipopolysaccharide (LPS) of Gram-negative bacteria is a potent inducer of the host innate immune system. TLR4, in association with MD-2, is the archetype receptor for LPS although B. pseudomallei LPS has been previously identified as a TLR2 agonist. We examined TLR signaling induced by B. pseudomallei, B. pseudomallei LPS, and B. pseudomallei lipid A using gain-of-function transfection assays of NF-κB activation and studies of TLR-deficient macrophages. Results: In HEK293 cells transfected with murine or human TLRs, CD14, and MD-2, heat-killed B. pseudomallei activated TLR2 (in combination with TLR1 or TLR6) and TLR4. B. pseudomallei LPS and lipid A activated TLR4 and this TLR4-mediated signaling required MD-2. In TLR2-/- macrophages, stimulation with heat-killed B. pseudomallei augmented TNF-α and MIP-2 production whereas in TLR4-/- cells, TNF-α, MIP-2, and IL-10 production was reduced. Cytokine production by macrophages stimulated with B. pseudomallei LPS or lipid A was entirely dependent on TLR4 but was increased in the absence of TLR2. TLR adaptor molecule MyD88 strongly regulated TNF-α production in response to heat-killed B. pseudomallei. Conclusion: B. pseudomallei activates TLR2 and TLR4. In the presence of MD-2, B. pseudomallei LPS and lipid A are TLR4 ligands. Although the macrophage cytokine response to B. pseudomallei LPS or lipid A is completely dependent on TLR4, in TLR2-/- macrophages stimulated with B. pseudomallei, B. pseudomallei LPS or lipid A, cytokine production is augmented. Other MyD88-dependent signaling pathways may also be important in the host response to B. pseudomallei infection. These findings provide new insights into critical mechanisms of host defense in melioidosis. http://www.biomedcentral.com/1471-2172/9/46 T Eoin West, Robert K Ernst, Malinka J Jansson-Hutson and Shawn J Skerrett BMC Immunology 2008, 9:46 Number of accesses: 274 2008-08-08 doi:10.1186/1471-2172-9-46 BMC Immunology 1471-2172 9 46 2008-08-08