scholarly journals The evolution of innate immune receptors: investigating the diversity, distribution, and phylogeny of immune recognition across eukaryotes

2021 ◽  
Author(s):  
Katherine M. Buckley ◽  
Jeffrey A. Yoder
Keyword(s):  
Innate Immune ◽  
Immune Recognition ◽  
Immune Receptors

scholarly journals Effects of innate immune receptor stimulation on extracellular α-synuclein uptake and degradation by brain resident cells

2021 ◽  
Author(s):  
Changyoun Kim ◽  
Somin Kwon ◽  
Michiyo Iba ◽  
Brian Spencer ◽  
Edward Rockenstein ◽  
...  
Keyword(s):  
Degradation Kinetics ◽  
Morphological Changes ◽  
Direct Interaction ◽  
Innate Immune ◽  
Pathological Feature ◽  
Tlr2 Expression ◽  
Immune Receptors ◽  
Age Related ◽  
Stimulation Of

AbstractSynucleinopathies are age-related neurological disorders characterized by the progressive deposition of α-synuclein (α-syn) aggregates and include Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Although cell-to-cell α-syn transmission is thought to play a key role in the spread of α-syn pathology, the detailed mechanism is still unknown. Neuroinflammation is another key pathological feature of synucleinopathies. Previous studies have identified several immune receptors that mediate neuroinflammation in synucleinopathies, such as Toll-like receptor 2 (TLR2). However, the species of α-syn aggregates varies from study to study, and how different α-syn aggregate species interact with innate immune receptors has yet to be addressed. Therefore, we investigated whether innate immune receptors can facilitate the uptake of different species of α-syn aggregates. Here, we examined whether stimulation of TLRs could modulate the cellular uptake and degradation of α-syn fibrils despite a lack of direct interaction. We observed that stimulation of TLR2 in vitro accelerated α-syn fibril uptake in neurons and glia while delaying the degradation of α-syn in neurons and astrocytes. Internalized α-syn was rapidly degraded in microglia regardless of whether TLR2 was stimulated. However, cellular α-syn uptake and degradation kinetics were not altered by TLR4 stimulation. In addition, upregulation of TLR2 expression in a synucleinopathy mouse model increased the density of Lewy-body-like inclusions and induced morphological changes in microglia. Together, these results suggest that cell type-specific modulation of TLR2 may be a multifaceted and promising therapeutic strategy for synucleinopathies; inhibition of neuronal and astroglial TLR2 decreases pathogenic α-syn transmission, but activation of microglial TLR2 enhances microglial extracellular α-syn clearance.

scholarly journals CD46 Plays a Key Role in Tailoring Innate Immune Recognition of Apoptotic and Necrotic Cells

2005 ◽  
Vol 280 (43) ◽  
pp. 36342-36354 ◽  
Author(s):  
Kristina Elward ◽  
Mark Griffiths ◽  
Masashi Mizuno ◽  
Claire L. Harris ◽  
Jim W. Neal ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Apoptotic Cell ◽  
Membrane Attack Complex ◽  
Factor H ◽  
Innate Immune ◽  
Immune Recognition ◽  
Alternative Pathways ◽  
Complement Regulator ◽  
Complement C1q

Complement is the canonical innate immune system involved in host defense and tissue repair with the clearance of cell debris. In contrast to the robust armory mounted against microbial nonself-pathogens, complement is selectively activated on altered self (i.e. apoptotic and necrotic cells) to instruct the safe demise by poorly characterized mechanisms. Our data shed new light on the role of complement C1q in sensing nucleic acids (NA) rapidly exposed on apoptotic Jurkat T cell membranes and in driving C3 opsonization but without the lytic membrane attack complex. DNA/RNase-treated apoptotic cells failed to activate complement. We found that several other apoptotic cell models, including senescent keratinocytes, ionophore-treated sperm cells, and CMK-derived platelets, stained for cleaved caspase 3 were rapidly losing the key complement regulator CD46. CD46 from nuclear and membrane stores was found to cluster into blebs and shed into microparticles together with NA, phosphatidylserine, C1q, and factor H. Classical and alternative pathways of complement were involved in the recognition of H2O2-treated necrotic cells. Membrane attack complex was detected on necrotic cells possibly as a result of CD46 and CD59 shedding into soluble forms. Our data highlight a novel and universal paradigm whereby the complement innate immune system is using two synergistic strategies with the recognition of altered self-NA and missing self-CD46 signals to instruct and tailor the efficient removal of apoptotic and necrotic cells in immunoprivileged sites.

Dysregulation of innate immune receptors on neutrophils in chronic granulomatous disease

2008 ◽  
Vol 121 (2) ◽  
pp. 375-382.e9 ◽  
Author(s):  
Dominik Hartl ◽  
Natalie Lehmann ◽  
Florian Hoffmann ◽  
Annette Jansson ◽  
Andreas Hector ◽  
...  
Keyword(s):  
Chronic Granulomatous Disease ◽  
Innate Immune ◽  
Granulomatous Disease ◽  
Immune Receptors
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