ABSTRACT
Cholera toxin (CT), a bacterial exotoxin composed of one A subunit (CTA) and five B subunits (CTB), functions as an immune adjuvant. CTB can induce production of interleukin-1ß (IL-1ß), a proinflammatory cytokine, in synergy with a lipopolysaccharide (LPS), from resident peritoneal macrophages (RPMs) through the pyrin and NLRP3 inflammasomes. However, how CTB or CT activates these inflammasomes in the macrophages has been unclear. Here, we clarify the roles of inositol-requiring enzyme 1 alpha (IRE1α), an endoplasmic reticulum (ER) stress sensor, in CT-induced IL-1ß production in RPMs. In RPMs, CTB is incorporated into the ER and induces ER stress responses, depending on GM1, a cell membrane ganglioside. IRE1α-deficient RPMs show a significant impairment of CT- or CTB-induced IL-1ß production, indicating that IRE1α is required for CT- or CTB-induced IL-1ß production in RPMs. This study demonstrates the critical roles of IRE1α in activation of both NLRP3 and pyrin inflammasomes in tissue-resident macrophages.
Subject(s)
Cholera Toxin , Endoplasmic Reticulum Stress , Endoribonucleases , Interleukin-1beta , Protein Serine-Threonine Kinases , Interleukin-1beta/metabolism , Animals , Endoribonucleases/metabolism , Protein Serine-Threonine Kinases/metabolism , Endoplasmic Reticulum Stress/drug effects , Mice , Cholera Toxin/pharmacology , Cholera Toxin/metabolism , Inflammasomes/metabolism , Mice, Inbred C57BL , Macrophages/metabolism , Macrophages/drug effects , Macrophages, Peritoneal/metabolism , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/immunology , Lipopolysaccharides/pharmacology , Endoplasmic Reticulum/metabolismABSTRACT
Dendritic cells (DC) play critical roles in linking innate and adaptive immunity. DC are heterogenous and there are subsets with various distinct functions. One DC subset, conventional type 1 DC (cDC1), can be defined by expression of CD8α/CD103 in mice and CD141 in humans, or by expression of a chemokine receptor, XCR1, which is a conserved marker in both mice and human. cDC1 are characterized by high ability to ingest dying cells and to cross-present antigens for generating cytotoxic CD8 T cell responses. Through these activities, cDC1 play crucial roles in immune responses against infectious pathogens or tumors. Meanwhile, cDC1 involvement in homeostatic situations is not fully understood. Analyses by using mutant mice, in which cDC1 are ablated in vivo, revealed that cDC1 are critical for maintaining intestinal immune homeostasis. Here, we review the homeostatic roles of cDC1, focusing upon intestinal immunity.
Subject(s)
Cross-Priming , Dendritic Cells , Animals , CD8-Positive T-Lymphocytes , Homeostasis , Mice , Receptors, Chemokine/metabolismABSTRACT
Formation mechanisms of hollow manganese hexacyanoferrate (Mn-HCF) particles have been investigated. Mn-HCF particles, which were precipitated by mixing an aqueous solution of K3[Fe(CN)6] with MnCl2 in the presence of sodium citrate, could be converted into a hollow structure just by washing with distilled water. The powder X-ray diffractometry suggested that the as-prepared particle has a core/shell morphology with different crystal structures: cubic-core and monoclinic-shell. The time evolutions of the particle size and shell thickness indicated that the core was rapidly (but not instantaneously) formed at the initial stage of the precipitation process, followed by a slower shell growth. In addition, the solubility of the cubic core was estimated to be about 2.5 times higher than that of the monoclinic shell, resulting in the preferential dissolution of the interior of the particle by the washing process. The formation procedure has been used to construct multiple-shell hollow Mn-HCF particles containing up to quadruple separated nesting shells by associating an additional growth technique.
