Nematode-induced interference with vaccination efficacy targets follicular T helper cell induction and is preserved after termination of infection.
One-third of the human population is infected with parasitic worms. To avoid being eliminated, these parasites actively dampen the immune response of their hosts. This immune modulation also suppresses immune responses to third-party antigens such as vaccines. Here, we used Litomosoides sigmodontis-...
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ftdoajarticles:oai:doaj.org/article:c68e99b0d61e438c9e609ad1c6bd6ceb 2023-05-15T15:13:46+02:00 Nematode-induced interference with vaccination efficacy targets follicular T helper cell induction and is preserved after termination of infection. Irma Haben Wiebke Hartmann Minka Breloer 2014-09-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003170 https://doaj.org/article/c68e99b0d61e438c9e609ad1c6bd6ceb EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4177885?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003170 https://doaj.org/article/c68e99b0d61e438c9e609ad1c6bd6ceb PLoS Neglected Tropical Diseases, Vol 8, Iss 9, p e3170 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003170 2022-12-31T14:53:35Z One-third of the human population is infected with parasitic worms. To avoid being eliminated, these parasites actively dampen the immune response of their hosts. This immune modulation also suppresses immune responses to third-party antigens such as vaccines. Here, we used Litomosoides sigmodontis-infected BALB/c mice to analyse nematode-induced interference with vaccination. Chronic nematode infection led to complete suppression of the humoral response to thymus-dependent vaccination. Thereby the numbers of antigen-specific B cells as well as the serum immunoglobulin (Ig) G titres were reduced. TH2-associated IgG1 and TH1-associated IgG2 responses were both suppressed. Thus, nematode infection did not bias responses towards a TH2 response, but interfered with Ig responses in general. We provide evidence that this suppression indirectly targeted B cells via accessory T cells as number and frequency of vaccine-induced follicular B helper T cells were reduced. Moreover, vaccination using model antigens that stimulate Ig response independently of T helper cells was functional in nematode-infected mice. Using depletion experiments, we show that CD4+Foxp3+ regulatory T cells did not mediate the suppression of Ig response during chronic nematode infection. Suppression was induced by fourth stage larvae, immature adults and mature adults, and increased with the duration of the infection. By contrast, isolated microfilariae increased IgG2a responses to vaccination. This pro-inflammatory effect of microfilariae was overruled by the simultaneous presence of adults. Strikingly, a reduced humoral response was still observed if vaccination was performed more than 16 weeks after termination of L. sigmodontis infection. In summary, our results suggest that vaccination may not only fail in helminth-infected individuals, but also in individuals with a history of previous helminth infections. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 8 9 e3170 |
institution |
Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Irma Haben Wiebke Hartmann Minka Breloer Nematode-induced interference with vaccination efficacy targets follicular T helper cell induction and is preserved after termination of infection. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
One-third of the human population is infected with parasitic worms. To avoid being eliminated, these parasites actively dampen the immune response of their hosts. This immune modulation also suppresses immune responses to third-party antigens such as vaccines. Here, we used Litomosoides sigmodontis-infected BALB/c mice to analyse nematode-induced interference with vaccination. Chronic nematode infection led to complete suppression of the humoral response to thymus-dependent vaccination. Thereby the numbers of antigen-specific B cells as well as the serum immunoglobulin (Ig) G titres were reduced. TH2-associated IgG1 and TH1-associated IgG2 responses were both suppressed. Thus, nematode infection did not bias responses towards a TH2 response, but interfered with Ig responses in general. We provide evidence that this suppression indirectly targeted B cells via accessory T cells as number and frequency of vaccine-induced follicular B helper T cells were reduced. Moreover, vaccination using model antigens that stimulate Ig response independently of T helper cells was functional in nematode-infected mice. Using depletion experiments, we show that CD4+Foxp3+ regulatory T cells did not mediate the suppression of Ig response during chronic nematode infection. Suppression was induced by fourth stage larvae, immature adults and mature adults, and increased with the duration of the infection. By contrast, isolated microfilariae increased IgG2a responses to vaccination. This pro-inflammatory effect of microfilariae was overruled by the simultaneous presence of adults. Strikingly, a reduced humoral response was still observed if vaccination was performed more than 16 weeks after termination of L. sigmodontis infection. In summary, our results suggest that vaccination may not only fail in helminth-infected individuals, but also in individuals with a history of previous helminth infections. |
format |
Article in Journal/Newspaper |
author |
Irma Haben Wiebke Hartmann Minka Breloer |
author_facet |
Irma Haben Wiebke Hartmann Minka Breloer |
author_sort |
Irma Haben |
title |
Nematode-induced interference with vaccination efficacy targets follicular T helper cell induction and is preserved after termination of infection. |
title_short |
Nematode-induced interference with vaccination efficacy targets follicular T helper cell induction and is preserved after termination of infection. |
title_full |
Nematode-induced interference with vaccination efficacy targets follicular T helper cell induction and is preserved after termination of infection. |
title_fullStr |
Nematode-induced interference with vaccination efficacy targets follicular T helper cell induction and is preserved after termination of infection. |
title_full_unstemmed |
Nematode-induced interference with vaccination efficacy targets follicular T helper cell induction and is preserved after termination of infection. |
title_sort |
nematode-induced interference with vaccination efficacy targets follicular t helper cell induction and is preserved after termination of infection. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0003170 https://doaj.org/article/c68e99b0d61e438c9e609ad1c6bd6ceb |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 9, p e3170 (2014) |
op_relation |
http://europepmc.org/articles/PMC4177885?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003170 https://doaj.org/article/c68e99b0d61e438c9e609ad1c6bd6ceb |
op_doi |
https://doi.org/10.1371/journal.pntd.0003170 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
8 |
container_issue |
9 |
container_start_page |
e3170 |
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1766344288767049728 |