| http://purl.uniprot.org/citations/15107845 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15107845 | http://www.w3.org/2000/01/rdf-schema#comment | "Macrophages play host to Leishmania major, a parasite that causes leishmaniasis in 500,000 people annually. Macrophage-expressed CD40, a costimulatory molecule, induces interleukin-12 (IL-12)-dependent and interferon-gamma (IFN-gamma)-dependent host-protective immune responses to Leishmania and other intracellular pathogens. Paradoxically, IL-10, another CD40-induced cytokine in macrophages, promotes Leishmania infection. How CD40 signaling regulates the secretion of these two counteractive cytokines remains unknown. Here we show that weak CD40 signals induce extracellular stress-related kinase-1/2 (ERK-1/2)-dependent IL-10 expression, whereas stronger signals induce p38 mitogen-activated protein kinase (p38MAPK)-dependent IL-12 production. p38MAPK and ERK-1/2 therefore have counter-regulatory actions. Leishmania skews CD40 signaling toward ERK-1/2, inducing IL-10, which inhibits activation of CD40-induced p38MAPK and expression of inducible nitric oxide synthase-2 (iNOS-2) and IL-12. ERK-1/2 inhibition or IL-10 neutralization restores CD40-induced p38MAPK activation and parasite killing in macrophages and the BALB/c mouse, a susceptible host. These data uncover a new immune evasion strategy, whereby Leishmania differentially modulates CD40-engaged, reciprocally functioning signaling modules, and provide a new conceptual framework for immune homeostasis."xsd:string |
| http://purl.uniprot.org/citations/15107845 | http://purl.org/dc/terms/identifier | "doi:10.1038/nm1045"xsd:string |
| http://purl.uniprot.org/citations/15107845 | http://purl.uniprot.org/core/author | "Saha B."xsd:string |
| http://purl.uniprot.org/citations/15107845 | http://purl.uniprot.org/core/author | "Awasthi A."xsd:string |
| http://purl.uniprot.org/citations/15107845 | http://purl.uniprot.org/core/author | "Mathur R.K."xsd:string |
| http://purl.uniprot.org/citations/15107845 | http://purl.uniprot.org/core/author | "Ramanamurthy B."xsd:string |
| http://purl.uniprot.org/citations/15107845 | http://purl.uniprot.org/core/author | "Wadhone P."xsd:string |
| http://purl.uniprot.org/citations/15107845 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/15107845 | http://purl.uniprot.org/core/name | "Nat Med"xsd:string |
| http://purl.uniprot.org/citations/15107845 | http://purl.uniprot.org/core/pages | "540-544"xsd:string |
| http://purl.uniprot.org/citations/15107845 | http://purl.uniprot.org/core/title | "Reciprocal CD40 signals through p38MAPK and ERK-1/2 induce counteracting immune responses."xsd:string |
| http://purl.uniprot.org/citations/15107845 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/15107845 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15107845 |
| http://purl.uniprot.org/citations/15107845 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/15107845 |
| http://purl.uniprot.org/uniprot/#_P63085-mappedCitation-15107845 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15107845 |
| http://purl.uniprot.org/uniprot/#_A2A5L7-mappedCitation-15107845 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15107845 |
| http://purl.uniprot.org/uniprot/#_A0A3B2WAZ7-mappedCitation-15107845 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15107845 |
| http://purl.uniprot.org/uniprot/#_A0A3B2WB60-mappedCitation-15107845 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15107845 |
| http://purl.uniprot.org/uniprot/#_A0A338P736-mappedCitation-15107845 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15107845 |
| http://purl.uniprot.org/uniprot/#_A0A338P781-mappedCitation-15107845 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15107845 |
| http://purl.uniprot.org/uniprot/#_A0A0U1RPX4-mappedCitation-15107845 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15107845 |
| http://purl.uniprot.org/uniprot/#_A0A0U1RPZ0-mappedCitation-15107845 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15107845 |
| http://purl.uniprot.org/uniprot/#_B2KF34-mappedCitation-15107845 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15107845 |
| http://purl.uniprot.org/uniprot/#_D3Z3G6-mappedCitation-15107845 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15107845 |