Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Infection drives meningeal engraftment by inflammatory monocytes that impairs CNS immunity.

ABSTRACT: Tissue macrophages have an embryonic origin and can be replenished in some tissues under steady-state conditions by blood monocytes. However, little is known about the residency and properties of infiltrating monocytes after an inflammatory challenge. The meninges of the central nervous system (CNS) are populated by a dense network of macrophages that act as resident immune sentinels. Here we show that, following lymphocytic choriomeningitis virus infection, resident meningeal macrophages (MMs) acquired viral antigen and interacted directly with infiltrating cytotoxic T lymphocytes, which led to macrophage depletion. Concurrently, the meninges were infiltrated by inflammatory monocytes that engrafted the meningeal niche and remained in situ for months after viral clearance. This engraftment led to interferon-γ-dependent functional changes in the pool of MMs, including loss of bacterial and immunoregulatory sensors. Collectively, these data indicate that peripheral monocytes can engraft the meninges after an inflammatory challenge, imprinting the compartment with long-term defects in immune function.

SUBMITTER: Rua R

PROVIDER: S-EPMC6481670 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-03-06 | GSE108648 | GEO

Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity [II]

Project description:Tissue-resident macrophages have an embryonic origin, but are replenished under steady state conditions in some tissues by blood monocytes that can adopt genotypic and phenotypic features of the residents. However, little is known about the residency and functional properties of infiltrating macrophages after an inflammatory challenge. The meninges of the central nervous system (CNS) are populated by a dense network of specialized macrophages that act as resident immune sentinels. Here we show that following lymphocytic choriomeningitis virus infection resident meningeal macrophages become activated by innate inflammatory cytokines, acquire viral antigen, and interact directly with infiltrating cytotoxic T lymphocytes (CTL), which leads to their depletion. Concurrently, the meninges are heavily infiltrated by peripherally-derived inflammatory monocytes that engraft the meningeal niche and remain in situ for months after viral clearance. This engraftment leads to phenotypic and functional changes in the pool of resident meningeal macrophages that depends in part on IFNγ signaling. These changes include loss of bacterial and immunoregulatory sensors that impede subsequent CNS immune reactions. Collectively, these data indicate that peripheral monocytes can engraft the meninges after an inflammatory challenge, imprinting the compartment with long-term defects in immune function.

2019-03-06 | GSE108647 | GEO

Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity [I]

2019-03-06 | GSE108467 | GEO

Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity

Project description:Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity

| PRJNA428167 | ENA

Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity [II]

Project description:Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity [II]

| PRJNA428169 | ENA

Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity [I]

Project description:Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity [I]

| PRJNA427333 | ENA

Cytomegalovirus impairs antiviral CD8+ T cell immunity by recruiting inflammatory monocytes.

Project description:Inflammatory monocytes are key early responders to infection that contribute to pathogen-host interactions in diverse ways. Here, we report that the murine cytomegalovirus-encoded CC chemokine, MCK2, enhanced CCR2-dependent recruitment of these cells to modulate antiviral immunity, impairing virus-specific CD8(+) T cell expansion and differentiation into effector cytotoxic T lymphocytes, thus reducing the capacity to eliminate viral antigen-bearing cells and slowing viral clearance. Adoptive transfer of inflammatory monocytes into Ccr2(-/-)Ccl2(-/-) mice impaired virus antigen-specific clearance. Cytomegalovirus therefore enhances a natural CCR2-dependent immune regulatory network to modulate adaptive immunity via nitric oxide production, reminiscent of the monocytic subtype of myeloid-derived suppressor cells primarily implicated in cancer immunomodulation.

| S-EPMC3412053 | biostudies-literature

Low-grade inflammatory polarization of monocytes impairs wound healing.

Project description:Impaired wound healing often accompanies low-grade inflammatory conditions, during which circulating levels of subclinical super-low-dose endotoxin may persist. Low-grade inflammatory monocyte polarization may occur during chronic inflammation and deter effective wound repair. However, little is understood about the potential mechanisms of monocyte polarization by sustained insult of subclinical super-low-dose endotoxin. We observed that super-low-dose endotoxin preferentially programmes a low-grade inflammatory monocyte state in vitro and in vivo, as represented by the elevated population of CD11b(+) Ly6C(high) monocytes and sustained expression of CCR5. Mechanistically, super-low-dose endotoxin caused cellular stress, altered lysosome function and increased the transcription factor IRF5. TUDCA, a potent inhibitor of cellular stress, effectively blocked monocyte polarization and improved wound healing in mice injected with super-low-dose endotoxin. Our data revealed the polarization of low-grade inflammatory monocytes by sustained endotoxin challenge, its underlying mechanisms and a potential intervention strategy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

| S-EPMC4760849 | biostudies-literature

Inflammatory monocytes promote pre-engraftment syndrome and tocilizumab can therapeutically limit pathology in patients.

Project description:Unrelated cord blood transplantation (UCBT) is an effective treatment for hematopoietic disorders. However, this attractive approach is frequently accompanied by pre-engraftment syndrome (PES), severe cases of PES are associated with enhanced mortality and morbidity, but the pathogenesis of PES remains unclear. Here we show that GM-CSF produced by cord blood-derived inflammatory monocytes drives PES pathology, and that monocytes are the main source of IL-6 during PES. Further, we report the outcome of a single arm, single-center clinical study of tocilizumab in the treatment of steroid-refractory severe PES patients (www.chictr.org.cn ChiCTR1800015472). The study met the primary outcome measure since none of the patients was nonrelapse death during the 100 days follow-up. The study also met key secondary outcomes measures of neutrophil engraftment and hematopoiesis. These findings offer a therapeutic strategy with which to tackle PES and improve nonrelapse mortality.

| S-EPMC8260612 | biostudies-literature

Inflammatory monocytes orchestrate innate antifungal immunity in the lung.

Project description:Aspergillus fumigatus is an environmental fungus that causes invasive aspergillosis (IA) in immunocompromised patients. Although -CC-chemokine receptor-2 (CCR2) and Ly6C-expressing inflammatory monocytes (CCR2?Mo) and their derivatives initiate adaptive pulmonary immune responses, their role in coordinating innate immune responses in the lung remain poorly defined. Using conditional and antibody-mediated cell ablation strategies, we found that CCR2?Mo and monocyte-derived dendritic cells (Mo-DCs) are essential for innate defense against inhaled conidia. By harnessing fluorescent Aspergillus reporter (FLARE) conidia that report fungal cell association and viability in vivo, we identify two mechanisms by which CCR2?Mo and Mo-DCs exert innate antifungal activity. First, CCR2?Mo and Mo-DCs condition the lung inflammatory milieu to augment neutrophil conidiacidal activity. Second, conidial uptake by CCR2?Mo temporally coincided with their differentiation into Mo-DCs, a process that resulted in direct conidial killing. Our findings illustrate both indirect and direct functions for CCR2?Mo and their derivatives in innate antifungal immunity in the lung.

| S-EPMC3930594 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data