Modulation of CXCL10 activity as a therapeutic target of ocular toxoplasmosis in diabetic mice
© Indian Society for Parasitology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law..
Ocular toxoplasmosis is likely the most common cause of infectious posterior uveitis worldwide. CXCL10 chemokine has an important role in the maintenance of the T-cell response and the control of Toxoplasma gondii in the eye during chronic infection. Drugs that can modulate the chemokine activity could be effective against the parasite. In this work, CXCL10 local retinal expression was investigated in a diabetic mouse model with ocular toxoplasmosis for the first time. In addition, the efficacy of naphthoquinones and quinolones was compared to spiramycin (SP) in treating the infection and modulating the chemokine expression. Our results revealed that chloroquine (CQ) achieved the best results regarding the reduction of cerebral cyst burden (84.36%), improving the retinal histopathological changes, cellular infiltrates, and vasculitis significantly (P < 0.005), and balancing the strong CXCL10 expression caused by the infection. Buparvaquone-treated mice showed a significant percentage of reduction of brain cysts (76.25%), moderate improvement of histopathology, and mild to moderate CXCL10 expression. While SP showed the least efficacy against the parasite in the eye in the form of mild improvement of histopathological changes and downregulation of retinal chemokine expression with the least reduction rate of cerebral parasitic burden (57%). In conclusion, Optimal control of pathogens probably needs a balanced immune response with an optimum expression of chemokines. So, targeting the modulation of retinal CXCL10 may eventually be beneficial in the management of ocular toxoplasmosis plus its potential to act as a marker for predictive local immunological response during the infection.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:48 |
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| Enthalten in: |
Journal of parasitic diseases : official organ of the Indian Society for Parasitology - 48(2024), 1 vom: 28. März, Seite 33-45 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ahmed Fahmy, Mennat-Elrahman [VerfasserIn] |
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| Links: |
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| Themen: |
Buparvaquone |
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| Anmerkungen: |
Date Revised 06.03.2024 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1007/s12639-023-01635-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Ocular toxoplasmosis is likely the most common cause of infectious posterior uveitis worldwide. CXCL10 chemokine has an important role in the maintenance of the T-cell response and the control of Toxoplasma gondii in the eye during chronic infection. Drugs that can modulate the chemokine activity could be effective against the parasite. In this work, CXCL10 local retinal expression was investigated in a diabetic mouse model with ocular toxoplasmosis for the first time. In addition, the efficacy of naphthoquinones and quinolones was compared to spiramycin (SP) in treating the infection and modulating the chemokine expression. Our results revealed that chloroquine (CQ) achieved the best results regarding the reduction of cerebral cyst burden (84.36%), improving the retinal histopathological changes, cellular infiltrates, and vasculitis significantly (P < 0.005), and balancing the strong CXCL10 expression caused by the infection. Buparvaquone-treated mice showed a significant percentage of reduction of brain cysts (76.25%), moderate improvement of histopathology, and mild to moderate CXCL10 expression. While SP showed the least efficacy against the parasite in the eye in the form of mild improvement of histopathological changes and downregulation of retinal chemokine expression with the least reduction rate of cerebral parasitic burden (57%). In conclusion, Optimal control of pathogens probably needs a balanced immune response with an optimum expression of chemokines. So, targeting the modulation of retinal CXCL10 may eventually be beneficial in the management of ocular toxoplasmosis plus its potential to act as a marker for predictive local immunological response during the infection | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Buparvaquone | |
| 650 | 4 | |a Chloroquine | |
| 650 | 4 | |a Diabetic mice | |
| 650 | 4 | |a Ocular toxoplasmosis | |
| 650 | 4 | |a Retinal CXCL10 | |
| 700 | 1 | |a Abdel-Aal, Amany Ahmed |e verfasserin |4 aut | |
| 700 | 1 | |a Shalaby, Maisa Ahmed |e verfasserin |4 aut | |
| 700 | 1 | |a Issa, Ragaa |e verfasserin |4 aut | |
| 700 | 1 | |a Badawi, Manal |e verfasserin |4 aut | |
| 700 | 1 | |a Fouly, Marwa A |e verfasserin |4 aut | |
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