Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Rynkiewicz, Evelyn C, Clerc, Melanie, Babayan, Simon A, Pedersen, Amy B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
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
_version_ 1783471755123228672
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
work_keys_str_mv AT rynkiewiczevelync variationinlocalandsystemicproinflammatoryimmunemarkersofwildwoodmiceafteranthelmintictreatment
AT clercmelanie variationinlocalandsystemicproinflammatoryimmunemarkersofwildwoodmiceafteranthelmintictreatment
AT babayansimona variationinlocalandsystemicproinflammatoryimmunemarkersofwildwoodmiceafteranthelmintictreatment
AT pedersenamyb variationinlocalandsystemicproinflammatoryimmunemarkersofwildwoodmiceafteranthelmintictreatment