Interferon-Inducible CXC Chemokines Directly Contribute to Host Defense against Inhalational Anthrax in a Murine Model of Infection

Chemokines have been found to exert direct, defensin-like antimicrobial activity in vitro, suggesting that, in addition to orchestrating cellular accumulation and activation, chemokines may contribute directly to the innate host response against infection. No observations have been made, however, demonstrating direct chemokine-mediated promotion of host defense in vivo. Here, we show that the murine interferon-inducible CXC chemokines CXCL9, CXCL10, and CXCL11 each exert direct antimicrobial effects in vitro against Bacillus anthracis Sterne strain spores and bacilli including disruptions in spore germination and marked reductions in spore and bacilli viability as assessed using CFU determination and a fluorometric assay of metabolic activity. Similar chemokine-mediated antimicrobial activity was also observed against fully virulent Ames strain spores and encapsulated bacilli. Moreover, antibody-mediated neutralization of these CXC chemokines in vivo was found to significantly increase host susceptibility to pulmonary B. anthracis infection in a murine model of inhalational anthrax with disease progression characterized by systemic bacterial dissemination, toxemia, and host death. Neutralization of the shared chemokine receptor CXCR3, responsible for mediating cellular recruitment in response to CXCL9, CXCL10, and CXCL11, was not found to increase host susceptibility to inhalational anthrax. Taken together, our data demonstrate a novel, receptor-independent antimicrobial role for the interferon-inducible CXC chemokines in pulmonary innate immunity in vivo. These data also support an immunomodulatory approach for effectively treating and/or preventing pulmonary B. anthracis infection, as well as infections caused by pathogenic and potentially, multi-drug resistant bacteria including other spore-forming organisms

The specificity and the development of social-emotional competence in a multi-ethnic-classroom

<p>Abstract</p> <p>Background</p> <p>Ethnic diversity in schools increases due to globalization. Thus, the children's social-emotional competence development must be considered in the context of a multi-ethnic classroom.</p> <p>Methods</p> <p>In this study, the social-emotional competence of 65 Asian-American and Latin-American children was observed at the beginning and the end of their kindergarten year.</p> <p>Results</p> <p>Initially, significant differences existed among these ethnic groups in respect to moral reasoning. Furthermore, the male children showed more dysregulated aggression but the female children implemented more moral reasoning than their male counterparts. These ethnic specificities did not disappear over the course of the year. In addition, a significant change in avoidance strategies as well as expressed emotions in the narrative took place over the course of one year.</p> <p>Conclusion</p> <p>Ethnic specificity in social-emotional competence does exist independent of gender at the beginning as well as at the end of the kindergarten year in a multi-ethnic kindergarten classroom.</p

Interaction between CXCR4 and CCL20 Pathways Regulates Tumor Growth

The chemokine receptor CXCR4 and its ligand CXCL12 is overexpressed in the majority of tumors and is critically involved in the development and metastasis of these tumors. CXCR4 is expressed in malignant tumor cells whereas its ligand SDF-1 (CXCL12) is expressed mainly by cancer associated fibroblasts (CAF). Similarly to CXCR4, the chemokine CCL20 is overexpressed in variety of tumors; however its role and regulation in tumors is not fully clear. Here, we show that the chemokine receptor CXCR4 stimulates the production of the chemokine CCL20 and that CCL20 stimulates the proliferation and adhesion to collagen of various tumor cells. Furthermore, overexpression of CCL20 in tumor cells promotes growth and adhesion in vitro and increased tumor growth and invasiveness in vivo. Moreover, neutralizing antibodies to CCL20 inhibit the in vivo growth of tumors that either overexpress CXCR4 or CCL20 or naturally express CCL20. These results reveal a role for CCL20 in CXCR4-dependent and -independent tumor growth and suggest a therapeutic potential for CCL20 and CCR6 antagonists in the treatment of CXCR4- and CCL20-dependent malignancies

Expression of mucosal chemokines TECK/CCL25 and MEC/CCL28 during fetal development of the ovine mucosal immune system

CCL25/TECK and CCL28/MEC are CC chemokines primarily expressed in thymic dendritic cells and mucosal epithelial cells. The cognate receptors of CCL25 and CCL28, CCR9 and CCR10, respectively, are mainly expressed on T and B lymphocytes. In human, mouse and pig, CCL25 and CCL28 play a key role in the segregation and the compartmentalization of the mucosal immune system through recruitment of immune cells to specific locations. However, little is known about their role in the ontogeny of the mucosal immune system during fetal development. In the present paper, we report the cloning and the sequencing of ovine CCL25, CCL28, CCR9 and CCR10 and the subsequent assessment of their mRNA expression by q-polymerase chain reaction in several tissues, including thymus, gut-associated lymphoid tissue and mammary gland, from young and adult sheep and in the fetal lamb during the development of the immune system. CCL25 mRNA was highly expressed in thymus and gut while CCL28 mRNA was more expressed in large intestine, trachea, tonsils and mammary gland, especially at the end of gestation. These results are consistent with observations in other species suggesting similar roles for these chemokines in sheep. In fetuses, mRNA of CCL25, CCL28 and their receptors are expressed early in the thymus and mucosal tissues, including the small intestine and the nasal mucosa. Furthermore, their expression increased towards the end of gestation. Consequently, we hypothesize that CCL25 and CCL28 play an important role in the lymphocyte colonization of fetal tissues, enabling the development of a functional immune system

CSF protein profiling using Multiplex Immuno-assay : A potential new diagnostic tool for leptomeningeal metastases.

Contains fulltext : 49861.pdf (publisher's version ) (Closed access)OBJECTIVE: The diagnosis of leptomeningeal metastases (LM) is based on clinical symptoms, magnetic resonance imaging (MRI) of brain and spine and cytological analysis of cerebrospinal fluid (CSF). The clinical picture of LM is highly variable and both cytological CSF analysis and contrast-enhanced MRI are limited in sensitivity. More sensitive tools are needed to diagnose LM. We measured a profile of proteins involved in adhesion and inflammation in the CSF of LM and control patients and determined their potential diagnostic value for LM. PATIENTS AND METHODS: Using Multiplex Immuno-Assay (MIA), the CSF concentrations of nine soluble adhesion molecules, cyto- and chemokines were measured in patients with cytologically proven LM (n=57) and control patients with a systemic malignancy (n=20), aseptic/viral meningitis (n=11) or other (non-)neurological diseases (n=19). RESULTS: We found high CSF levels of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), soluble Intercellular Adhesion Molecule-1 (sICAM-1), Interleukin-8 (IL-8), Pulmonary and Activation Regulated Chemokine (PARC), Interleukin-18 (IL-18) and Interferon-gamma inducible protein (IP-10) in patients with LM. The CSF protein profile in LM patients differed significantly from the profile found in control patients. Multivariate logistic regression and ROC analysis showed that the MIA-measured CSF protein profile has an additive discriminating value for LM above standard CSF parameters. A combination of total protein, glucose, IL-8, PARC and IP-10 CSF levels proved to be most discriminative between LM and non-LM patients. CONCLUSION: Our results warrant a prospective study to determine whether a CSF protein profile, including IL-8, PARC and IP-10 has diagnostic value compared with CSF cytology, the golden standard for LM