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Variation in Local and Systemic Pro-Inflammatory Immune Markers of Wild Wood Mice after Anthelmintic Treatment
The immune system represents a host’s main defense against infection to parasites and pathogens. In the wild, a host’s response to immune challenges can vary due to physiological condition, demography (age, sex), and coinfection by other parasites or pathogens. These sources of variation, which are...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863754/ https://www.ncbi.nlm.nih.gov/pubmed/31368489 http://dx.doi.org/10.1093/icb/icz136 |
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author | Rynkiewicz, Evelyn C Clerc, Melanie Babayan, Simon A Pedersen, Amy B |
author_facet | Rynkiewicz, Evelyn C Clerc, Melanie Babayan, Simon A Pedersen, Amy B |
author_sort | Rynkiewicz, Evelyn C |
collection | PubMed |
description | The immune system represents a host’s main defense against infection to parasites and pathogens. In the wild, a host’s response to immune challenges can vary due to physiological condition, demography (age, sex), and coinfection by other parasites or pathogens. These sources of variation, which are intrinsic to natural populations, can significantly impact the strength and type of immune responses elicited after parasite exposure and infection. Importantly, but often neglected, a host’s immune response can also vary within the individual, across tissues and between local and systemic scales. Consequently, how a host responds at each scale may impact its susceptibility to concurrent and subsequent infections. Here we analyzed how characteristics of hosts and their parasite infections drive variation in the pro-inflammatory immune response in wild wood mice (Apodemus sylvaticus) at both the local and systemic scale by experimentally manipulating within-host parasite communities through anthelmintic drug treatment. We measured concentrations of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) produced in vitro in response to a panel of toll-like receptor agonists at the local (mesenteric lymph nodes [MLNs]) and systemic (spleen) scales of individuals naturally infected with two gastrointestinal parasites, the nematode Heligmosomoides polygyrus and the protozoan Eimeria hungaryensis. Anthelmintic-treated mice had a 20-fold lower worm burden compared to control mice, as well as a four-fold higher intensity of the non-drug targeted parasite E. hungaryensis. Anthelmintic treatment differentially impacted levels of TNF-α expression in males and females at the systemic and local scales, with treated males producing higher, and treated females lower, levels of TNF-α, compared to control mice. Also, TNF-α was affected by host age, at the local scale, with MLN cells of young, treated mice producing higher levels of TNF-α than those of old, treated mice. Using complementary, but distinct, measures of inflammation measured across within-host scales allowed us to better assess the wood mouse immune response to changes in parasite infection dynamics after anthelmintic treatment. This same approach could be used to understand helminth infections and responses to parasite control measures in other systems in order to gain a broader view of how variation impacts the immune response. |
format | Online Article Text |
id | pubmed-6863754 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-68637542019-11-25 Variation in Local and Systemic Pro-Inflammatory Immune Markers of Wild Wood Mice after Anthelmintic Treatment Rynkiewicz, Evelyn C Clerc, Melanie Babayan, Simon A Pedersen, Amy B Integr Comp Biol S2 The scale of sickness: how immune variation across space and species affects infectious disease dynamics The immune system represents a host’s main defense against infection to parasites and pathogens. In the wild, a host’s response to immune challenges can vary due to physiological condition, demography (age, sex), and coinfection by other parasites or pathogens. These sources of variation, which are intrinsic to natural populations, can significantly impact the strength and type of immune responses elicited after parasite exposure and infection. Importantly, but often neglected, a host’s immune response can also vary within the individual, across tissues and between local and systemic scales. Consequently, how a host responds at each scale may impact its susceptibility to concurrent and subsequent infections. Here we analyzed how characteristics of hosts and their parasite infections drive variation in the pro-inflammatory immune response in wild wood mice (Apodemus sylvaticus) at both the local and systemic scale by experimentally manipulating within-host parasite communities through anthelmintic drug treatment. We measured concentrations of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) produced in vitro in response to a panel of toll-like receptor agonists at the local (mesenteric lymph nodes [MLNs]) and systemic (spleen) scales of individuals naturally infected with two gastrointestinal parasites, the nematode Heligmosomoides polygyrus and the protozoan Eimeria hungaryensis. Anthelmintic-treated mice had a 20-fold lower worm burden compared to control mice, as well as a four-fold higher intensity of the non-drug targeted parasite E. hungaryensis. Anthelmintic treatment differentially impacted levels of TNF-α expression in males and females at the systemic and local scales, with treated males producing higher, and treated females lower, levels of TNF-α, compared to control mice. Also, TNF-α was affected by host age, at the local scale, with MLN cells of young, treated mice producing higher levels of TNF-α than those of old, treated mice. Using complementary, but distinct, measures of inflammation measured across within-host scales allowed us to better assess the wood mouse immune response to changes in parasite infection dynamics after anthelmintic treatment. This same approach could be used to understand helminth infections and responses to parasite control measures in other systems in order to gain a broader view of how variation impacts the immune response. Oxford University Press 2019-11 2019-08-01 /pmc/articles/PMC6863754/ /pubmed/31368489 http://dx.doi.org/10.1093/icb/icz136 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | S2 The scale of sickness: how immune variation across space and species affects infectious disease dynamics Rynkiewicz, Evelyn C Clerc, Melanie Babayan, Simon A Pedersen, Amy B Variation in Local and Systemic Pro-Inflammatory Immune Markers of Wild Wood Mice after Anthelmintic Treatment |
title | Variation in Local and Systemic Pro-Inflammatory Immune Markers of Wild Wood Mice after Anthelmintic Treatment |
title_full | Variation in Local and Systemic Pro-Inflammatory Immune Markers of Wild Wood Mice after Anthelmintic Treatment |
title_fullStr | Variation in Local and Systemic Pro-Inflammatory Immune Markers of Wild Wood Mice after Anthelmintic Treatment |
title_full_unstemmed | Variation in Local and Systemic Pro-Inflammatory Immune Markers of Wild Wood Mice after Anthelmintic Treatment |
title_short | Variation in Local and Systemic Pro-Inflammatory Immune Markers of Wild Wood Mice after Anthelmintic Treatment |
title_sort | variation in local and systemic pro-inflammatory immune markers of wild wood mice after anthelmintic treatment |
topic | S2 The scale of sickness: how immune variation across space and species affects infectious disease dynamics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863754/ https://www.ncbi.nlm.nih.gov/pubmed/31368489 http://dx.doi.org/10.1093/icb/icz136 |
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