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Praziquantel Treatment of Schistosoma mansoni Infected Mice Renders Them Less Susceptible to Reinfection

Beyond transient control of the infection, additional benefits of mass drug administration of praziquantel in endemic communities have been suggested in communities but not mechanistically investigated experimentally. The present study sought to evaluate the additional and hitherto unreported benefi...

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Autores principales: Nono, Justin Komguep, Mpotje, Thabo, Mosala, Paballo, Aziz, Nada Abdel, Musaigwa, Fungai, Hlaka, Lerato, Spangenberg, Thomas, Brombacher, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703194/
https://www.ncbi.nlm.nih.gov/pubmed/34956183
http://dx.doi.org/10.3389/fimmu.2021.748387
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author Nono, Justin Komguep
Mpotje, Thabo
Mosala, Paballo
Aziz, Nada Abdel
Musaigwa, Fungai
Hlaka, Lerato
Spangenberg, Thomas
Brombacher, Frank
author_facet Nono, Justin Komguep
Mpotje, Thabo
Mosala, Paballo
Aziz, Nada Abdel
Musaigwa, Fungai
Hlaka, Lerato
Spangenberg, Thomas
Brombacher, Frank
author_sort Nono, Justin Komguep
collection PubMed
description Beyond transient control of the infection, additional benefits of mass drug administration of praziquantel in endemic communities have been suggested in communities but not mechanistically investigated experimentally. The present study sought to evaluate the additional and hitherto unreported benefits of repeated mass drug administration of praziquantel. We used a tractable mouse model of Schistosoma mansoni infection to assess the effects of repeated infection-treatment cycles on the host susceptibility to reinfection. Parasitaemia was assessed by quantification of Schistosoma egg burden in liver tissues and morbidity was followed up by histological observation of liver lesions by microscopy and using biochemical measurement of liver transaminases. Immune responses were further determined by serum probing of schistosoma-specific antibodies, cytokines and quantification of liver cellular and soluble mediator responses by flow cytometry and ELISA, respectively. At similar ages and comparable gender distribution, groups of mice undergoing higher number of infections treatment cycles over a longer period, remained susceptible to reinfection by the parasite, as judged by the presence of eggs and the associated increasing pathology in the liver tissues. However, notably, there was a clear and significantly higher propensity to lower egg burden upon reinfection when compared to counterparts undergoing a lower number of infection-treatment cycles. This relative reduction of susceptibility to infection was paralleled by a more robust humoral response against parasite antigens, elevated serum IL-4 and liver cytokines. Of note, praziquantel treatment of infected mice left them at a higher baseline of serum IL-4, IgE and liver cytokines but lower CD4+ T cell -derived cytokines when compared to infected non-treated mice supporting an immunological treatment-induced advantage of previously infected mice over naïve mice and infected/not treated mice. Notably, repeated infection-treatment cycles did not preclude the infection-driven aggravation of collagen deposition in the livers over time and was corroborated by a more robust local production of inflammatory cytokines in the most exposed livers. Taken together, our data reveal that treatment of S. mansoni-infected hosts with praziquantel rewires the immune system to a conformation less permissive to subsequent reinfection in mice. Provided the data are translatable from mouse to human, our findings may provide mechanistic support to the potential benefits of more frequent MDAs in high transmission areas to allow rapid acquisition of protective immunity against reinfection.
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spelling pubmed-87031942021-12-25 Praziquantel Treatment of Schistosoma mansoni Infected Mice Renders Them Less Susceptible to Reinfection Nono, Justin Komguep Mpotje, Thabo Mosala, Paballo Aziz, Nada Abdel Musaigwa, Fungai Hlaka, Lerato Spangenberg, Thomas Brombacher, Frank Front Immunol Immunology Beyond transient control of the infection, additional benefits of mass drug administration of praziquantel in endemic communities have been suggested in communities but not mechanistically investigated experimentally. The present study sought to evaluate the additional and hitherto unreported benefits of repeated mass drug administration of praziquantel. We used a tractable mouse model of Schistosoma mansoni infection to assess the effects of repeated infection-treatment cycles on the host susceptibility to reinfection. Parasitaemia was assessed by quantification of Schistosoma egg burden in liver tissues and morbidity was followed up by histological observation of liver lesions by microscopy and using biochemical measurement of liver transaminases. Immune responses were further determined by serum probing of schistosoma-specific antibodies, cytokines and quantification of liver cellular and soluble mediator responses by flow cytometry and ELISA, respectively. At similar ages and comparable gender distribution, groups of mice undergoing higher number of infections treatment cycles over a longer period, remained susceptible to reinfection by the parasite, as judged by the presence of eggs and the associated increasing pathology in the liver tissues. However, notably, there was a clear and significantly higher propensity to lower egg burden upon reinfection when compared to counterparts undergoing a lower number of infection-treatment cycles. This relative reduction of susceptibility to infection was paralleled by a more robust humoral response against parasite antigens, elevated serum IL-4 and liver cytokines. Of note, praziquantel treatment of infected mice left them at a higher baseline of serum IL-4, IgE and liver cytokines but lower CD4+ T cell -derived cytokines when compared to infected non-treated mice supporting an immunological treatment-induced advantage of previously infected mice over naïve mice and infected/not treated mice. Notably, repeated infection-treatment cycles did not preclude the infection-driven aggravation of collagen deposition in the livers over time and was corroborated by a more robust local production of inflammatory cytokines in the most exposed livers. Taken together, our data reveal that treatment of S. mansoni-infected hosts with praziquantel rewires the immune system to a conformation less permissive to subsequent reinfection in mice. Provided the data are translatable from mouse to human, our findings may provide mechanistic support to the potential benefits of more frequent MDAs in high transmission areas to allow rapid acquisition of protective immunity against reinfection. Frontiers Media S.A. 2021-12-10 /pmc/articles/PMC8703194/ /pubmed/34956183 http://dx.doi.org/10.3389/fimmu.2021.748387 Text en Copyright © 2021 Nono, Mpotje, Mosala, Aziz, Musaigwa, Hlaka, Spangenberg and Brombacher https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Nono, Justin Komguep
Mpotje, Thabo
Mosala, Paballo
Aziz, Nada Abdel
Musaigwa, Fungai
Hlaka, Lerato
Spangenberg, Thomas
Brombacher, Frank
Praziquantel Treatment of Schistosoma mansoni Infected Mice Renders Them Less Susceptible to Reinfection
title Praziquantel Treatment of Schistosoma mansoni Infected Mice Renders Them Less Susceptible to Reinfection
title_full Praziquantel Treatment of Schistosoma mansoni Infected Mice Renders Them Less Susceptible to Reinfection
title_fullStr Praziquantel Treatment of Schistosoma mansoni Infected Mice Renders Them Less Susceptible to Reinfection
title_full_unstemmed Praziquantel Treatment of Schistosoma mansoni Infected Mice Renders Them Less Susceptible to Reinfection
title_short Praziquantel Treatment of Schistosoma mansoni Infected Mice Renders Them Less Susceptible to Reinfection
title_sort praziquantel treatment of schistosoma mansoni infected mice renders them less susceptible to reinfection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703194/
https://www.ncbi.nlm.nih.gov/pubmed/34956183
http://dx.doi.org/10.3389/fimmu.2021.748387
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