Single-cell transcriptome profiling and the use of AID deficient mice reveal that B cell activation combined with antibody class switch recombination and somatic hypermutation do not benefit the control of experimental trypanosomosis.

Salivarian trypanosomes are extracellular protozoan parasites causing infections in a wide range of mammalian hosts, with Trypanosoma evansi having the widest geographic distribution, reaching territories far outside Africa and occasionally even Europe. Besides causing the animal diseases, T. evansi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hang Thi Thu Nguyen, Robin B Guevarra, Stefan Magez, Magdalena Radwanska
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/24d2e7ad39d341cdb4bdec069474422e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:24d2e7ad39d341cdb4bdec069474422e
record_format	dspace
spelling	oai:doaj.org-article:24d2e7ad39d341cdb4bdec069474422e2021-12-02T19:59:57ZSingle-cell transcriptome profiling and the use of AID deficient mice reveal that B cell activation combined with antibody class switch recombination and somatic hypermutation do not benefit the control of experimental trypanosomosis.1553-73661553-737410.1371/journal.ppat.1010026https://doaj.org/article/24d2e7ad39d341cdb4bdec069474422e2021-11-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1010026https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Salivarian trypanosomes are extracellular protozoan parasites causing infections in a wide range of mammalian hosts, with Trypanosoma evansi having the widest geographic distribution, reaching territories far outside Africa and occasionally even Europe. Besides causing the animal diseases, T. evansi can cause atypical Human Trypanosomosis. The success of this parasite is attributed to its capacity to evade and disable the mammalian defense response. To unravel the latter, we applied here for the first time a scRNA-seq analysis on splenocytes from trypanosome infected mice, at two time points during infection, i.e. just after control of the first parasitemia peak (day 14) and a late chronic time point during infection (day 42). This analysis was combined with flow cytometry and ELISA, revealing that T. evansi induces prompt activation of splenic IgM+CD1d+ Marginal Zone and IgMIntIgD+ Follicular B cells, coinciding with an increase in plasma IgG2c Ab levels. Despite the absence of follicles, a rapid accumulation of Aicda+ GC-like B cells followed first parasitemia peak clearance, accompanied by the occurrence of Xbp1+ expressing CD138+ plasma B cells and Tbx21+ atypical CD11c+ memory B cells. Ablation of immature CD93+ bone marrow and Vpreb3+Ly6d+Ighm+ expressing transitional spleen B cells prevented mature peripheral B cell replenishment. Interestingly, AID-/- mice that lack the capacity to mount anti-parasite IgG responses, exhibited a superior defense level against T. evansi infections. Here, elevated natural IgMs were able to exert in vivo and in vitro trypanocidal activity. Hence, we conclude that in immune competent mice, trypanosomosis associated B cell activation and switched IgG production is rapidly induced by T. evansi, facilitating an escape from the detrimental natural IgM killing activity, and resulting in increased host susceptibility. This unique role of IgM and its anti-trypanosome activity are discussed in the context of the dilemma this causes for the future development of anti-trypanosome vaccines.Hang Thi Thu NguyenRobin B GuevarraStefan MagezMagdalena RadwanskaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 11, p e1010026 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Hang Thi Thu Nguyen Robin B Guevarra Stefan Magez Magdalena Radwanska Single-cell transcriptome profiling and the use of AID deficient mice reveal that B cell activation combined with antibody class switch recombination and somatic hypermutation do not benefit the control of experimental trypanosomosis.
description	Salivarian trypanosomes are extracellular protozoan parasites causing infections in a wide range of mammalian hosts, with Trypanosoma evansi having the widest geographic distribution, reaching territories far outside Africa and occasionally even Europe. Besides causing the animal diseases, T. evansi can cause atypical Human Trypanosomosis. The success of this parasite is attributed to its capacity to evade and disable the mammalian defense response. To unravel the latter, we applied here for the first time a scRNA-seq analysis on splenocytes from trypanosome infected mice, at two time points during infection, i.e. just after control of the first parasitemia peak (day 14) and a late chronic time point during infection (day 42). This analysis was combined with flow cytometry and ELISA, revealing that T. evansi induces prompt activation of splenic IgM+CD1d+ Marginal Zone and IgMIntIgD+ Follicular B cells, coinciding with an increase in plasma IgG2c Ab levels. Despite the absence of follicles, a rapid accumulation of Aicda+ GC-like B cells followed first parasitemia peak clearance, accompanied by the occurrence of Xbp1+ expressing CD138+ plasma B cells and Tbx21+ atypical CD11c+ memory B cells. Ablation of immature CD93+ bone marrow and Vpreb3+Ly6d+Ighm+ expressing transitional spleen B cells prevented mature peripheral B cell replenishment. Interestingly, AID-/- mice that lack the capacity to mount anti-parasite IgG responses, exhibited a superior defense level against T. evansi infections. Here, elevated natural IgMs were able to exert in vivo and in vitro trypanocidal activity. Hence, we conclude that in immune competent mice, trypanosomosis associated B cell activation and switched IgG production is rapidly induced by T. evansi, facilitating an escape from the detrimental natural IgM killing activity, and resulting in increased host susceptibility. This unique role of IgM and its anti-trypanosome activity are discussed in the context of the dilemma this causes for the future development of anti-trypanosome vaccines.
format	article
author	Hang Thi Thu Nguyen Robin B Guevarra Stefan Magez Magdalena Radwanska
author_facet	Hang Thi Thu Nguyen Robin B Guevarra Stefan Magez Magdalena Radwanska
author_sort	Hang Thi Thu Nguyen
title	Single-cell transcriptome profiling and the use of AID deficient mice reveal that B cell activation combined with antibody class switch recombination and somatic hypermutation do not benefit the control of experimental trypanosomosis.
title_short	Single-cell transcriptome profiling and the use of AID deficient mice reveal that B cell activation combined with antibody class switch recombination and somatic hypermutation do not benefit the control of experimental trypanosomosis.
title_full	Single-cell transcriptome profiling and the use of AID deficient mice reveal that B cell activation combined with antibody class switch recombination and somatic hypermutation do not benefit the control of experimental trypanosomosis.
title_fullStr	Single-cell transcriptome profiling and the use of AID deficient mice reveal that B cell activation combined with antibody class switch recombination and somatic hypermutation do not benefit the control of experimental trypanosomosis.
title_full_unstemmed	Single-cell transcriptome profiling and the use of AID deficient mice reveal that B cell activation combined with antibody class switch recombination and somatic hypermutation do not benefit the control of experimental trypanosomosis.
title_sort	single-cell transcriptome profiling and the use of aid deficient mice reveal that b cell activation combined with antibody class switch recombination and somatic hypermutation do not benefit the control of experimental trypanosomosis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/24d2e7ad39d341cdb4bdec069474422e
work_keys_str_mv	AT hangthithunguyen singlecelltranscriptomeprofilingandtheuseofaiddeficientmicerevealthatbcellactivationcombinedwithantibodyclassswitchrecombinationandsomatichypermutationdonotbenefitthecontrolofexperimentaltrypanosomosis AT robinbguevarra singlecelltranscriptomeprofilingandtheuseofaiddeficientmicerevealthatbcellactivationcombinedwithantibodyclassswitchrecombinationandsomatichypermutationdonotbenefitthecontrolofexperimentaltrypanosomosis AT stefanmagez singlecelltranscriptomeprofilingandtheuseofaiddeficientmicerevealthatbcellactivationcombinedwithantibodyclassswitchrecombinationandsomatichypermutationdonotbenefitthecontrolofexperimentaltrypanosomosis AT magdalenaradwanska singlecelltranscriptomeprofilingandtheuseofaiddeficientmicerevealthatbcellactivationcombinedwithantibodyclassswitchrecombinationandsomatichypermutationdonotbenefitthecontrolofexperimentaltrypanosomosis
_version_	1718375710062542848

Single-cell transcriptome profiling and the use of AID deficient mice reveal that B cell activation combined with antibody class switch recombination and somatic hypermutation do not benefit the control of experimental trypanosomosis.

Ejemplares similares