TLR9/MyD88/TRIF signaling activates host immune inhibitory CD200 in Leishmania infection

Sauter, Ismael Pretto; Madrid, Katerine G.; Assis, Josiane Betim de; Sá-Nunes, Anderson; Torrecilhas, Ana Claúdia; Staquicini, Daniela I.; Pasqualini, Renata; Arap, Wadih; Cortéz, Mauro

doi:10.1172/jci.insight.126207

Cited by 29 publications

(29 citation statements)

References 63 publications

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“…The survival and proliferation of Leishmania parasites rely on the modulation of macrophages' immune response [39]. For instance, L. amazonensis amastigotes release extracellular microvesicles containing DNA fragments that induce the expression of the surface glycoprotein CD200 in the host cell [40,41]. This mechanism is essential for parasite replication and disease progression [40,41].…”

Section: Discussionmentioning

confidence: 99%

“…For instance, L. amazonensis amastigotes release extracellular microvesicles containing DNA fragments that induce the expression of the surface glycoprotein CD200 in the host cell [40,41]. This mechanism is essential for parasite replication and disease progression [40,41]. Whether the low proliferation rate of intracellular parasites pre-treated with DODAB is related with a deficient macrophage modulation mechanism, such as the low secretion of microvesicles, remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

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Effect of DODAB Nano-Sized Cationic Bilayer Fragments against Leishmania amazonensis

et al. 2020

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The dioctadecyldimethylammonium bromide (DODAB) is a double-chained cationic lipid with potent bactericide and fungistatic activities; however, its toxicity on protozoan parasites is still unknown. Here, we show the antileishmanial activity of DODAB nano-sized cationic bilayer fragments on stationary-phase promastigotes and amastigotes of Leishmania amazonensis, the causative agent of cutaneous leishmaniasis. Upon treatment with DODAB, we analyzed the parasite surface zeta-potential, parasite viability, cellular structural modifications, and intracellular proliferation. The DODAB cytotoxic effect was dose-dependent, with a median effective concentration (EC50) of 25 µM for both life-cycle stages, comparable to the reported data for bacteria and fungi. The treatment with DODAB changed the membrane zeta-potential from negative to positive, compromised the parasite’s morphology, affected the cell size regulation, caused a loss of intracellular organelles, and probably dysregulated the plasma membrane permeability without membrane disruption. Moreover, the parasites that survived after treatment induced small parasitophorous vacuoles and failed to proliferate inside macrophages. In conclusion, DODAB displayed antileishmanial activity, and it remains to be elucidated how DODAB acts on the protozoan membrane. Understanding this mechanism can provide insights into the development of new parasite-control strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of DODAB Nano-Sized Cationic Bilayer Fragments against Leishmania amazonensis

et al. 2020

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“…Subsequent CD200:CD200R axis limits the innate immunity, through the inhibition of both classical macrophage activation and other myeloid-derived cells ( Figure 2 ). In this process, the key role plays adapter protein Dok2, that is additionally regulator for TLR4 [ 72 , 73 ]. Existence of such a negative loop feedback seems to significantly protect the host against the development of bacterial sepsis [ 73 , 74 ].…”

Section: Effect Of Cd200 and Cd200r Expression On Function Of Distmentioning

confidence: 99%

“…In the process of CD200 induction, TLRs or parasite DNA are also involved. Again, Leishmania amazonensis DNA activates TLR9, which in turn induces CD200 in parasite infected macrophages [ 73 ]. Infection of helminths ( Taenia crassiceps or Trypanosoma brucei brucei ) leads to overexpression of CD200R on macrophages M2, which in turn inhibits an innate immunity.…”

Section: Importance Of Cd200:cd200r Interactions In Transplantatiomentioning

confidence: 99%

CD200:CD200R Interactions and Their Importance in Immunoregulation

Kotwica-Mojzych

Jodłowska‐Jędrych

2021

IJMS

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The molecule CD200, described many years ago as a naturally occurring immunomodulatory agent, capable of regulating inflammation and transplant rejection, has attracted additional interest over the past years with the realization that it may also serve as an important marker for progressive malignancy. A large body of evidence also supports the hypothesis that this molecule can contribute to immunoregulation of, among other diseases, infection, autoimmune disease and allergy. New data have also come to light to characterize the receptors for CD200 (CD200R) and their potential mechanism(s) of action at the biochemical level, as well as the description of a novel natural antagonist of CD200, lacking the NH2-terminal region of the full-length molecule. Significant controversies exist concerning the relative importance of CD200 as a ligand for all reported CD200Rs. Nevertheless, some progress has been made in the identification of the structural constraints determining the interaction between CD200 and CD200R, and this information has in turn proved of use in developing novel small molecule agonists/antagonists of the interaction. The review below highlights many of these newer findings, and attempts to place them in the broad context of our understanding of the role of CD200-CD200R interactions in a variety of human diseases.

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“…Five days later, a pure population of T. cruzi trypomastigotes released in cell culture supernatants were harvested by centrifugation. L. amazonensis (IFLA/BR/67/PH8) was propagated as promastigotes at 26°C in M199 media supplemented with 5% penicillin/streptomycin, 0.1% hemin (25 mg/ml in 0.1N NaOH), 10 mM adenine and 10% FBS, pH 7.5 as previously described (Sauter et al, 2019). Antiprotozoal activity against T. cruzi was evaluated as previously described (Gutiérrez et al, 2013).…”

Section: Parasites and Cell Culturesmentioning

confidence: 99%

Chemical Profiling, Antioxidant, Anticholinesterase, and Antiprotozoal Potentials of Artemisia copa Phil. (Asteraceae)

Larrazábal

Fernández-Galleguillos

Palma-Ramírez

et al. 2020

Front. Pharmacol.

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Artemisia copa Phil. (Asteraceae) (known as copa-copa) is a native species of Chile used as an infusion in traditional medicine by Atacameños people in the Altiplano, highlands of northern Chile. In this research, we have investigated for the first time the cholinesterase inhibition potential against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and the chemical profiling of the infusions prepared from the aerial parts of A. copa by high resolution spectrometry. In addition, total phenolic, total flavonoid content, antioxidant (DPPH, FRAP, and ORAC) and antiprozoal activity were tested. Artemisia copa showed good inhibitory activity against AChE and BChE (3.92 ± 0.08 µg/ml and 44.13 ± 0.10 µg/ml). The infusion displayed a total phenolics content of 155.6 ± 2.9 mg of gallic acid equivalents/g and total flavonoid content of 5.5 ± 0.2 mg quercetin equivalents/g. Additionally, trypanocidal activity against Trypanosoma cruzi was found (LD50 of 131.8 µg/ml). Forty-seven metabolites were detected in the infusion of A. copa including several phenolic acids and flavonoids which were rapidly identified using ultrahigh performance liquid chromatography orbitrap mass spectrometry analysis (UHPLC-Orbitrap-MS) for chemical profiling. The major compounds identified in the infusions were studied by molecular docking against AChE and BChE. The UHPLC-MS fingerprints generated can be also used for the authentication of these endemic species. These findings reveal that A. copa infusions can be used as beverages with protective effects.

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TLR9/MyD88/TRIF signaling activates host immune inhibitory CD200 in Leishmania infection

Cited by 29 publications

References 63 publications

Effect of DODAB Nano-Sized Cationic Bilayer Fragments against Leishmania amazonensis

Effect of DODAB Nano-Sized Cationic Bilayer Fragments against Leishmania amazonensis

CD200:CD200R Interactions and Their Importance in Immunoregulation

Chemical Profiling, Antioxidant, Anticholinesterase, and Antiprotozoal Potentials of Artemisia copa Phil. (Asteraceae)

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