Rynkiewicz, E. C., Clerc, M., Babayan, S. A. and Pedersen, A. B. (2019) Variation in local and systemic pro-inflammatory immune markers of wild wood mice after anthelminthic treatment. Integrative and Comparative Biology, 59(5), pp. 1190-1202. (doi: 10.1093/icb/icz136) (PMID:31368489) (PMCID:PMC6863754)
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Abstract
The immune system represents a host’s main defence against infection to parasites and pathogens. In the wild, a host’s response to immune challenge 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 analysed 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 anthelminthic drug treatment. We measured concentrations of the pro-inflammatory cytokine TNF-α produced in vitro in response to a panel of TLR agonists at the local (mesenteric lymph nodes, MLN) and systemic (spleen) scales of individuals naturally infected with two gastrointestinal parasites, the nematode Heligmosomoides polygyrus and the protozoan Eimeria hungaryensis. Anthelminthic-treated mice had a 20-fold lower worm burden compared to control mice, as well as a 7-fold higher intensity of the non-drug targeted parasite E. hungaryensis. Anthelminthic 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 hosts. 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 anthelminthic 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.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was funded by the National Science Foundation (Postdoctoral Research Fellowship in Biology (DBI-1306608)) to ECR, a University of Edinburgh Torrance Bequest Scholarship to MC, Wellcome Trust ISSF grant [097821/Z/11/Z] to SB, a targeted Institute of Biodiversity, Animal Health and Comparative Medicine Research Fellowship to SB, a Wellcome Trust Strategic Grant for the Centre for Immunity Infection and Evolution (095831) to ABP, and a University of Edinburgh Chancellors Fellowship to ABP. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Babayan, Dr Simon |
| Authors: | Rynkiewicz, E. C., Clerc, M., Babayan, S. A., and Pedersen, A. B. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| Journal Name: | Integrative and Comparative Biology |
| Publisher: | Oxford University Press |
| ISSN: | 1540-7063 |
| ISSN (Online): | 1557-7023 |
| Published Online: | 01 August 2019 |
| Copyright Holders: | Copyright © 2019 The Authors |
| First Published: | First published in Integrative and Comparative Biology 59(5): 1190-1202 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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