Temporal trends of serotypes from invasive pneumococcal disease (IPD) in Spain from 1979 to September 2007 under antibiotic and vaccine pressure were analyzed. A significant trend in pneumococcal conjugate 7-valent vaccine (PCV7) serotypes (except serotype 4) was found, whereby the prevalence increased from the early 1980s and decreased in the 2000s for all but serotype 23F, which began decreasing in the late 1980s. Among the major non-PCV7 serotypes, a significant decrease was observed for serotypes 1, 5, and 7F in the 1980s. From the late 1990s, serotypes 1, 5, 6A, 7F, and 19A increased significantly, while serotypes 3 and 8 showed similar but nonsignificant trends over time. The incidence of IPD cases was 10.7/100,000 for the period 1996 to 2006, with reporting coverage ranging from 18% to 43%. A significant decrease in IPD incidence due to PCV7 serotypes was observed, while the incidence of non-PCV7 serotypes increased, with the consequence that there was no clear pattern in the overall incidence of IPD. Penicillin nonsusceptibility was correlated with the proportion of PCV7 serotypes. Erythromycin nonsusceptibility increased in association with long-half-life macrolide consumption and then decreased in 2004 to 2007. The increase in PCV7 serotypes and antibiotic nonsusceptibility related to antibiotic consumption in the 1980s and 1990s was reversed in the 2000s, probably as a result of PCV7 immunization. The decrease in IPD incidence due to PCV7 serotypes was mirrored by an increase in that of non-PCV7 serotypes. The impact of various preventive/therapeutic strategies on pneumococcal evolution is serotype dependent, and the dynamics remain unpredictable.

IntroductionThe identification of the lectin gene cluster at chromosome 19p13.2 1 has led to the realization that some C-type lectins are capable of mediating intercellular adhesion, pathogen-binding, and antigen internalization for induction of T cell responses. 2 The paradigmatic example of this type of lectin is dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), which efficiently internalizes antigens, 3 mediates dendritic cell intercellular adhesions, 4 and recognizes a wide range of microorganisms through binding to mannose-and Lewis-containing glycans. 5 C-type lectins on dendritic cells enhance their ability for pathogen recognition 6 and contribute to modulation of toll-like receptor (TLR)-initiated signals. 7 Consequently, the definition of the range of dendritic cell lectins and their binding specificities might provide adequate targets for immune intervention and prevention of pathogen entrance and spreading.The lectin gene cluster at chromosome 19p13.2 includes the genes encoding for the type II C-type lectins DC-SIGN, liver/lymph node-specific intercellular adhesion molecule-3-grabbing integrin (L-SIGN), CD23, and liver and lymph node sinusoidal endothelial cell C-type lectin (LSECtin). 1,4,8,9 DC-SIGN is expressed on myeloid dendritic cells, 4,10 and alternatively activated in vitro on macrophages. 11 In vivo it is found on interstitial dendritic cells, 12 a subset of CD14ϩ peripheral blood DC, 13 human microvascular endothelial cells, 8 and on synovial, placenta, lymph node, and alveolar macrophages. 14-16 By contrast, L-SIGN is exclusively expressed on endothelial cells of the liver, lymph nodes, and placenta, 17,18 but not on myeloid cells.The LSECtin (CLEC4G) gene is located between the CD23 and DC-SIGN genes with the three genes arranged in the same orientation. 9 LSECtin encodes a protein with a lectin domain followed by a 110-residue stalk region, a transmembrane domain, and a 31-residue cytoplasmic domain. 9 LSECtin has been previously detected on liver and lymph node sinusoidal endothelial cells at the protein and RNA level. 9 LSECtin functions as an attachment factor for Ebola virus and SARS, but it does not bind HIV or hepatitis C virus. 19 We now describe the expression of LSECtin isoforms in ex vivo isolated human peripheral blood and thymic dendritic cells as well as in dendritic cells and macrophages generated in vitro. LSECtin exhibits ligand-induced internalization, and its sugar recognition specificity differs from that of DC-SIGN. The presence of LSECtin on myeloid cells should therefore contribute to expanding their antigen-capture and pathogen-recognition capabilities. Materials and methodsThe study described was approved by the Centro de Investigaciones Biologicas (CSIC) Institutional Review Board. The study did not involve any direct contact with human subjects. Cell cultureHuman peripheral blood mononuclear cells were isolated from buffy coats from normal donors over a Lymphoprep (Nycomed Pharma, Oslo, Norway) gradient according to sta...

Intravenous Igs (IVIg) therapy is widely used as an immunomodulatory strategy in inflammatory pathologies and is suggested to promote cancer regression. Because progression of tumors depends on their ability to redirect the polarization state of tumor-associated macrophages (from M1/immunogenic/proinflammatory to M2/anti-inflammatory), we have evaluated whether IVIg limits tumor progression and dissemination through modulation of macrophage polarization. In vitro, IVIg inhibited proinflammatory cytokine production from M1 macrophages and induced a M2-to-M1 polarization switch on human and murine M2 macrophages. In vivo, IVIg modified the polarization of tumor-associated myeloid cells in a Fcεr1γ chain–dependent manner, modulated cytokine blood levels in tumor-bearing animals, and impaired tumor progression via FcγRIII (CD16), FcγRIV, and FcRγ engagement, the latter two effects being macrophage mediated. Therefore, IVIg immunomodulatory activity is dependent on the polarization state of the responding macrophages, and its ability to trigger a M2-to-M1 macrophage polarization switch might be therapeutically useful in cancer, in which proinflammatory or immunogenic functions should be promoted.