Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-11-2
pubmed:abstractText
Innate responses combine with adaptive immunity to generate the most effective form of anti-Aspergillus immune resistance. Whereas the pivotal role of dendritic cells in determining the balance between immunopathology and protective immunity to the fungus is well established, we determined that epithelial cells (ECs) also contributes to this balance. Mechanistically, EC-mediated protection occurred through a Toll-like receptor 3/Toll/IL-1 receptor domain-containing adaptor-inducing interferon (TLR3/TRIF)-dependent pathway converging on indoleamine 2,3-dioxygenase (IDO) via non-canonical nuclear factor-?B activation. Consistent with the high susceptibility of TRIF-deficient mice to pulmonary aspergillosis, bone marrow chimeric mice with TRIF unresponsive ECs exhibited higher fungal burdens and inflammatory pathology than control mice, underexpressed the IDO-dependent T helper 1/regulatory T cell (Th1/Treg) pathway and overexpressed the Th17 pathway with massive neutrophilic inflammation in the lungs. Further studies with interferon (IFN)-?, IDO or IL-17R unresponsive cells confirmed the dependency of immune tolerance to the fungus on the IFN-?/IDO/Treg pathway and of immune resistance on the MyD88 pathway controlling the fungal growth. Thus, distinct immune pathways contribute to resistance and tolerance to the fungus, to which the hematopoietic/non-hematopoietic compartments contribute through distinct, yet complementary, roles.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
2042-0226
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
459-70
pubmed:meshHeading
pubmed-meshheading:20835271-Adaptor Proteins, Vesicular Transport, pubmed-meshheading:20835271-Animals, pubmed-meshheading:20835271-Aspergillus fumigatus, pubmed-meshheading:20835271-Disease Susceptibility, pubmed-meshheading:20835271-Down-Regulation, pubmed-meshheading:20835271-Enzyme Activation, pubmed-meshheading:20835271-Epithelial Cells, pubmed-meshheading:20835271-Hematopoietic Stem Cell Transplantation, pubmed-meshheading:20835271-Hematopoietic System, pubmed-meshheading:20835271-Immune Tolerance, pubmed-meshheading:20835271-Indoleamine-Pyrrole 2,3,-Dioxygenase, pubmed-meshheading:20835271-Interferon-gamma, pubmed-meshheading:20835271-Interleukin-17, pubmed-meshheading:20835271-Kynurenine, pubmed-meshheading:20835271-Mice, pubmed-meshheading:20835271-Pneumonia, pubmed-meshheading:20835271-Pulmonary Aspergillosis, pubmed-meshheading:20835271-Receptors, Interleukin-17, pubmed-meshheading:20835271-Signal Transduction, pubmed-meshheading:20835271-T-Lymphocytes, Regulatory, pubmed-meshheading:20835271-Th17 Cells, pubmed-meshheading:20835271-Toll-Like Receptor 3, pubmed-meshheading:20835271-Up-Regulation
pubmed:year
2010
pubmed:articleTitle
Non-hematopoietic cells contribute to protective tolerance to Aspergillus fumigatus via a TRIF pathway converging on IDO.
pubmed:affiliation
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't