Adoptive Transfer of Immune Cells Into RAG2IL-2Rγ-Deficient Mice During Litomosoides sigmodontis Infection: A Novel Approach to Investigate Filarial-Specific Immune Responses

Despite long-term mass drug administration programmes, approximately 220 million people are still infected with filariae in endemic regions. Several research studies have characterized host immune responses but a major obstacle for research on human filariae has been the inability to obtain adult wo...

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Autores principales: Anna Wiszniewsky, Laura E. Layland, Kathrin Arndts, Lisa M. Wadephul, Ruth S. E. Tamadaho, Dennis Borrero-Wolff, Valerine C. Chunda, Chi Anizette Kien, Achim Hoerauf, Samuel Wanji, Manuel Ritter
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:dcf93911ea2a4f10bc20e763473f133b2021-11-18T05:34:57ZAdoptive Transfer of Immune Cells Into RAG2IL-2Rγ-Deficient Mice During Litomosoides sigmodontis Infection: A Novel Approach to Investigate Filarial-Specific Immune Responses1664-322410.3389/fimmu.2021.777860https://doaj.org/article/dcf93911ea2a4f10bc20e763473f133b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.777860/fullhttps://doaj.org/toc/1664-3224Despite long-term mass drug administration programmes, approximately 220 million people are still infected with filariae in endemic regions. Several research studies have characterized host immune responses but a major obstacle for research on human filariae has been the inability to obtain adult worms which in turn has hindered analysis on infection kinetics and immune signalling. Although the Litomosoides sigmodontis filarial mouse model is well-established, the complex immunological mechanisms associated with filarial control and disease progression remain unclear and translation to human infections is difficult, especially since human filarial infections in rodents are limited. To overcome these obstacles, we performed adoptive immune cell transfer experiments into RAG2IL-2Rγ-deficient C57BL/6 mice. These mice lack T, B and natural killer cells and are susceptible to infection with the human filaria Loa loa. In this study, we revealed a long-term release of L. sigmodontis offspring (microfilariae) in RAG2IL-2Rγ-deficient C57BL/6 mice, which contrasts to C57BL/6 mice which normally eliminate the parasites before patency. We further showed that CD4+ T cells isolated from acute L. sigmodontis-infected C57BL/6 donor mice or mice that already cleared the infection were able to eliminate the parasite and prevent inflammation at the site of infection. In addition, the clearance of the parasites was associated with Th17 polarization of the CD4+ T cells. Consequently, adoptive transfer of immune cell subsets into RAG2IL-2Rγ-deficient C57BL/6 mice will provide an optimal platform to decipher characteristics of distinct immune cells that are crucial for the immunity against rodent and human filarial infections and moreover, might be useful for preclinical research, especially about the efficacy of macrofilaricidal drugs.Anna WiszniewskyLaura E. LaylandLaura E. LaylandKathrin ArndtsLisa M. WadephulRuth S. E. TamadahoDennis Borrero-WolffValerine C. ChundaValerine C. ChundaChi Anizette KienChi Anizette KienAchim HoeraufAchim HoeraufAchim HoeraufSamuel WanjiSamuel WanjiManuel RitterFrontiers Media S.A.articleFilariaeLitomosoides sigmodontisCD4+ and CD8+ T cellsadoptive transferanti-filarial immunityTh17 polarizationImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Filariae
Litomosoides sigmodontis
CD4+ and CD8+ T cells
adoptive transfer
anti-filarial immunity
Th17 polarization
Immunologic diseases. Allergy
RC581-607
spellingShingle Filariae
Litomosoides sigmodontis
CD4+ and CD8+ T cells
adoptive transfer
anti-filarial immunity
Th17 polarization
Immunologic diseases. Allergy
RC581-607
Anna Wiszniewsky
Laura E. Layland
Laura E. Layland
Kathrin Arndts
Lisa M. Wadephul
Ruth S. E. Tamadaho
Dennis Borrero-Wolff
Valerine C. Chunda
Valerine C. Chunda
Chi Anizette Kien
Chi Anizette Kien
Achim Hoerauf
Achim Hoerauf
Achim Hoerauf
Samuel Wanji
Samuel Wanji
Manuel Ritter
Adoptive Transfer of Immune Cells Into RAG2IL-2Rγ-Deficient Mice During Litomosoides sigmodontis Infection: A Novel Approach to Investigate Filarial-Specific Immune Responses
description Despite long-term mass drug administration programmes, approximately 220 million people are still infected with filariae in endemic regions. Several research studies have characterized host immune responses but a major obstacle for research on human filariae has been the inability to obtain adult worms which in turn has hindered analysis on infection kinetics and immune signalling. Although the Litomosoides sigmodontis filarial mouse model is well-established, the complex immunological mechanisms associated with filarial control and disease progression remain unclear and translation to human infections is difficult, especially since human filarial infections in rodents are limited. To overcome these obstacles, we performed adoptive immune cell transfer experiments into RAG2IL-2Rγ-deficient C57BL/6 mice. These mice lack T, B and natural killer cells and are susceptible to infection with the human filaria Loa loa. In this study, we revealed a long-term release of L. sigmodontis offspring (microfilariae) in RAG2IL-2Rγ-deficient C57BL/6 mice, which contrasts to C57BL/6 mice which normally eliminate the parasites before patency. We further showed that CD4+ T cells isolated from acute L. sigmodontis-infected C57BL/6 donor mice or mice that already cleared the infection were able to eliminate the parasite and prevent inflammation at the site of infection. In addition, the clearance of the parasites was associated with Th17 polarization of the CD4+ T cells. Consequently, adoptive transfer of immune cell subsets into RAG2IL-2Rγ-deficient C57BL/6 mice will provide an optimal platform to decipher characteristics of distinct immune cells that are crucial for the immunity against rodent and human filarial infections and moreover, might be useful for preclinical research, especially about the efficacy of macrofilaricidal drugs.
format article
author Anna Wiszniewsky
Laura E. Layland
Laura E. Layland
Kathrin Arndts
Lisa M. Wadephul
Ruth S. E. Tamadaho
Dennis Borrero-Wolff
Valerine C. Chunda
Valerine C. Chunda
Chi Anizette Kien
Chi Anizette Kien
Achim Hoerauf
Achim Hoerauf
Achim Hoerauf
Samuel Wanji
Samuel Wanji
Manuel Ritter
author_facet Anna Wiszniewsky
Laura E. Layland
Laura E. Layland
Kathrin Arndts
Lisa M. Wadephul
Ruth S. E. Tamadaho
Dennis Borrero-Wolff
Valerine C. Chunda
Valerine C. Chunda
Chi Anizette Kien
Chi Anizette Kien
Achim Hoerauf
Achim Hoerauf
Achim Hoerauf
Samuel Wanji
Samuel Wanji
Manuel Ritter
author_sort Anna Wiszniewsky
title Adoptive Transfer of Immune Cells Into RAG2IL-2Rγ-Deficient Mice During Litomosoides sigmodontis Infection: A Novel Approach to Investigate Filarial-Specific Immune Responses
title_short Adoptive Transfer of Immune Cells Into RAG2IL-2Rγ-Deficient Mice During Litomosoides sigmodontis Infection: A Novel Approach to Investigate Filarial-Specific Immune Responses
title_full Adoptive Transfer of Immune Cells Into RAG2IL-2Rγ-Deficient Mice During Litomosoides sigmodontis Infection: A Novel Approach to Investigate Filarial-Specific Immune Responses
title_fullStr Adoptive Transfer of Immune Cells Into RAG2IL-2Rγ-Deficient Mice During Litomosoides sigmodontis Infection: A Novel Approach to Investigate Filarial-Specific Immune Responses
title_full_unstemmed Adoptive Transfer of Immune Cells Into RAG2IL-2Rγ-Deficient Mice During Litomosoides sigmodontis Infection: A Novel Approach to Investigate Filarial-Specific Immune Responses
title_sort adoptive transfer of immune cells into rag2il-2rγ-deficient mice during litomosoides sigmodontis infection: a novel approach to investigate filarial-specific immune responses
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/dcf93911ea2a4f10bc20e763473f133b
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