scholarly journals Bat Red Blood Cells express Nucleic Acid Sensing Receptors and bind RNA and DNA

2022 ◽  
Author(s):  
LK Metthew Lam ◽  
Jane Dobkin ◽  
Kaitlyn A. Eckart ◽  
Ian Gereg ◽  
Andrew DiSalvo ◽  
...  

Red blood cells (RBCs) demonstrate immunomodulatory capabilities through the expression of nucleic acid sensors. Little is known about bat RBCs, and no studies have examined the immune function of bat erythrocytes. Here we show that bat RBCs express the nucleic acid-sensing Toll-like receptors TLR7 and TLR9 and bind the nucleic acid ligands, single-stranded RNA, and CpG DNA. Collectively, these data suggest that, like human RBCs, bat erythrocytes possess immune function and may be reservoirs for nucleic acids. These findings provide unique insight into bat immunity and may uncover potential mechanisms by which virulent pathogens in humans are concealed in bats.

1953 ◽  
Vol 6 (2) ◽  
pp. 234 ◽  
Author(s):  
PR Whitfeld

Changes in� the nucleic acid content of the solid residue obtained by haemolysing the blood of mice infected with Plasmodium berghei have been examined. The residue from blood in which 25 per cent. of the red blood cells were parasitized contained 20-25 times as much ribosenucleic acid (RNA) and 12 times as much desoxyribosenucleic acid (DNA) as the residue from uninfected blood.


1976 ◽  
Vol 31 (3-4) ◽  
pp. 149-151 ◽  
Author(s):  
Dieter Auer ◽  
Gerhard Brandner

Abstract Human erythrocytes were suspended in Hank’s solution containing mammalian or viral DNA or RNA. After dialysis at 0 °C first against water and subsequently against Hank’s solution, and a further incubation at 37 °C , the erythrocytes were found to be loaded with the nucleic acids. The nucleic acid trapped in the erythrocytes exhibited up to 35 per cent of the external concentration.


2022 ◽  
Author(s):  
LK Metthew Lam ◽  
Rebecca L. Clements ◽  
Kaitlyn A. Eckart ◽  
Ariel R. Weisman ◽  
Andy E. Vaughan ◽  
...  

Red blood cells (RBCs) express the nucleic acid-sensing toll-like receptor 9 (TLR9) and bind CpG-containing DNA. However, whether human RBCs express other nucleic acid-sensing TLRs and bind RNA is unknown. Here we show that human RBCs express the RNA sensor, TLR7. TLR7 is present on the red cell membrane and associates with the RBC membrane protein Band 3. RBCs bind synthetic single-stranded RNA and RNA from pathogenic single-stranded RNA viruses. RNA acquisition by RBCs is attenuated by recombinant TLR7 and inhibitory oligonucleotides. Thus, RBCs may represent a previously unrecognized reservoir for RNA, although how RNA-binding by RBCs modulates the immune response has yet to be elucidated. These findings add to the growing list of non-gas exchanging RBC immune functions.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ratnasekhar Ch ◽  
Guillaume Rey ◽  
Sandipan Ray ◽  
Pawan K. Jha ◽  
Paul C. Driscoll ◽  
...  

AbstractCircadian clocks coordinate mammalian behavior and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms.


Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1600-1603 ◽  
Author(s):  
AT Hood ◽  
ME Fabry ◽  
F Costantini ◽  
RL Nagel ◽  
HL Shear

Previous studies from our laboratories have shown that transgenic mice expressing high levels of beta S globin are well-protected from Plasmodium chabaudi adami and partially protected against P berghei (Shear et al, Blood 81:222, 1993). We have now infected transgenic mice expressing low (39%), intermediate (57%), and high (75%) levels of beta S with the virulent strain of P yoelii (17XL) that appears to cause cerebral malaria. We find that the level of protection in these three groups of mice correlates positively with the level of beta S chain expression in the mice. Seven of nine mice expressing the high level of beta S recovered from infection, as did 7 of 9 mice expressing the intermediate level of beta S. Control mice and mice expressing the lower level of beta S all succumbed to infection. In mice expressing high and intermediate levels of beta S, parasites were found almost exclusively in reticulocytes during recovery, suggesting that mature red blood cells expressing beta S are more resistant than reticulocytes. These studies confirm epidemiologic data and offer insight into the mechanism of protection of sickle trait individuals against falciparum malaria.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Yukiko Kamiya ◽  
Tadashi Satoh ◽  
Atsuji Kodama ◽  
Tatsuya Suzuki ◽  
Keiji Murayama ◽  
...  

Abstract Xeno nucleic acids, which are synthetic analogues of natural nucleic acids, have potential for use in nucleic acid drugs and as orthogonal genetic biopolymers and prebiotic precursors. Although few acyclic nucleic acids can stably bind to RNA and DNA, serinol nucleic acid (SNA) and L-threoninol nucleic acid (L-aTNA) stably bind to them. Here we disclose crystal structures of RNA hybridizing with SNA and with L-aTNA. The heteroduplexes show unwound right-handed helical structures. Unlike canonical A-type duplexes, the base pairs in the heteroduplexes align perpendicularly to the helical axes, and consequently helical pitches are large. The unwound helical structures originate from interactions between nucleobases and neighbouring backbones of L-aTNA and SNA through CH–O bonds. In addition, SNA and L-aTNA form a triplex structure via C:G*G parallel Hoogsteen interactions with RNA. The unique structural features of the RNA-recognizing mode of L-aTNA and SNA should prove useful in nanotechnology, biotechnology, and basic research into prebiotic chemistry.


1976 ◽  
Vol 144 (6) ◽  
pp. 1695-1700 ◽  
Author(s):  
D Guerry ◽  
M A Kenna ◽  
A D Schrieber ◽  
R A Cooper

Human red blood cells sensitized with concanavalin A became bound to homologous peripheral blood monocytes. Binding occured at a concentration of 10(5) molecules of tetrameric Con A per red blood cell (RBC) and increased with additional Con A. RBC binding began within 5 min and was maximal at 90 min. Phagocytosis of sensitized RBCs was minimal. RBC attachment was prevented by 0.01 M alpha-methyl-D-mannopyranoside, and, once the RBC-monocyte rosette was established, bound RBCs were largely removed with this specific saccharide inhibitor of Con A. RBCs attached to monocytes became spherocytic and osmotically fragile. The recognition of concanavalin A (Con A)-coated RBCs was not mediated through the monocyte IgG-Fc receptor. These studies demonstrate that, like IgG and C3b, Con A is capable of mediating the binding of human RBCs to human monocytes. Red cells so bound are damaged at the monocyte surface.


1998 ◽  
Vol 275 (5) ◽  
pp. H1726-H1732 ◽  
Author(s):  
Randy S. Sprague ◽  
Mary L. Ellsworth ◽  
Alan H. Stephenson ◽  
Mary E. Kleinhenz ◽  
Andrew J. Lonigro

Recently, it was reported that rabbit and human red blood cells (RBCs) release ATP in response to mechanical deformation. Here we investigate the hypothesis that the activity of the cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ATP binding cassette, is required for deformation-induced ATP release from RBCs. Incubation of rabbit RBCs with either of two inhibitors of CFTR activity, glibenclamide (10 μM) or niflumic acid (20 μM), resulted in inhibition of deformation-induced ATP release. To demonstrate the contribution of CFTR to deformation-induced ATP release from human RBCs, cells from healthy humans, patients with cystic fibrosis (CF), or patients with chronic obstructive lung disease (COPD) unrelated to CF were studied. RBCs of healthy humans and COPD patients released ATP in response to mechanical deformation. In contrast, deformation of RBCs from patients with CF did not result in ATP release. We conclude that deformation-induced ATP release from rabbit and human RBCs requires CFTR activity, suggesting a previously unrecognized role for CFTR in the regulation of vascular resistance.


1980 ◽  
Vol 44 (1) ◽  
pp. 99-112 ◽  
Author(s):  
A. B. McAllan

1. Nucleic acids and breakdown products were estimated in digesta taken from different sites in the small intestines of slaughtered steers given different diets. Amounts passing different sites were compared using cellulose as a non-digestible marker. The validity of this marker was checked with chromic oxide in some experiments. In other experiments, nucleic acids or derivatives were infused into the proximal duodenum of steers receiving diets of approximately equal proportions of flaked maize and hay. The amounts disappearing during passage through the small intestine were estimated using polyethylene glycol (PEG) as a non- absorbable marker.2. In the slaughter experiments the amounts of nucleic acids entering the small intestine varied with the type of diet. RNA and DNA disappeared on average, to extents of 89% and 80% respectively between the abomasum and the terminal ileum, irrespective of the diet. RNA disappearance occurred almost entirely in the proximal quarter of the small intestine, whereas that of DNA extended further along the tract.3. Nucleic acid degradation in the upper small intestine was accompanied by the transient appearance of adenosine, guanosine and pyrimidine nucleosides. These products were in greatest concentration in digesta from the first quarter of the small intestine and had generally completely disappeared by the terminal ileum.4. Of the different substances infused into the small intestine, free nucleic acids were removed to extents greater than 97%, adenine, guanine and uracil had completely disappeared, thymine and xanthine to approximately 80% and 95% and hypoxanthine and cytosine to only 51% and 48% respectively. The nucleosides adenosine and cytidine were also completely removed in the small intestine but were replaced, in part, by the catabolic products inosine plus hypoxanthine or cytosine respectively. Other nucleosides were removed to approximately half the extent of the corresponding bases.5. Serum and urine allantoin and uric acid levels were related to the amounts of purines entering the small intestines in free or bound form.


2010 ◽  
Vol 207 (12) ◽  
pp. 2689-2701 ◽  
Author(s):  
Christoph L. Baumann ◽  
Irene M. Aspalter ◽  
Omar Sharif ◽  
Andreas Pichlmair ◽  
Stephan Blüml ◽  
...  

Recognition of pathogens by the innate immune system requires proteins that detect conserved molecular patterns. Nucleic acids are recognized by cytoplasmic sensors as well as by endosomal Toll-like receptors (TLRs). It has become evident that TLRs require additional proteins to be activated by their respective ligands. In this study, we show that CD14 (cluster of differentiation 14) constitutively interacts with the MyD88-dependent TLR7 and TLR9. CD14 was necessary for TLR7- and TLR9-dependent induction of proinflammatory cytokines in vitro and for TLR9-dependent innate immune responses in mice. CD14 associated with TLR9 stimulatory DNA in precipitation experiments and confocal imaging. The absence of CD14 led to reduced nucleic acid uptake in macrophages. Additionally, CD14 played a role in the stimulation of TLRs by viruses. Using various types of vesicular stomatitis virus, we showed that CD14 is dispensable for viral uptake but is required for the triggering of TLR-dependent cytokine responses. These data show that CD14 has a dual role in nucleic acid–mediated TLR activation: it promotes the selective uptake of nucleic acids, and it acts as a coreceptor for endosomal TLR activation.


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