Chronic helminth infection burden differentially affects haematopoietic cell development while ageing selectively impairs adaptive responses to infection

Babayan, S. A. , Sinclair, A., Duprez, J. S. and Selman, C. (2018) Chronic helminth infection burden differentially affects haematopoietic cell development while ageing selectively impairs adaptive responses to infection. Scientific Reports, 8, 3802. (doi:10.1038/s41598-018-22083-5) (PMID:29491449) (PMCID:PMC5830876)

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Abstract

Throughout the lifespan of an individual, the immune system undergoes complex changes while facing novel and chronic infections. Helminths, which infect over one billion people and impose heavy livestock productivity losses, typically cause chronic infections by avoiding and suppressing host immunity. Yet, how age affects immune responses to lifelong parasitic infection is poorly understood. To disentangle the processes involved, we employed supervised statistical learning techniques to identify which factors among haematopoietic stem and progenitor cells (HSPC), and both innate and adaptive responses regulate parasite burdens and how they are affected by host age. Older mice harboured greater numbers of the parasites’ offspring than younger mice. Protective immune responses that did not vary with age were dominated by HSPC, while ageing specifically eroded adaptive immunity, with reduced numbers of naïve T cells, poor T cell responsiveness to parasites, and impaired antibody production. We identified immune factors consistent with previously-reported immune responses to helminths, and also revealed novel interactions between helminths and HSPC maturation. Our approach thus allowed disentangling the concurrent effects of ageing and infection across the full maturation cycle of the immune response and highlights the potential of such approaches to improve understanding of the immune system within the whole organism.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Sinclair, Miss Amy and Babayan, Dr Simon and Selman, Professor Colin
Authors: Babayan, S. A., Sinclair, A., Duprez, J. S., and Selman, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN:2045-2322
ISSN (Online):2045-2322
Published Online:28 February 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Scientific Reports 8:3802
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
658171Dissecting variation in host responsiveness to a recombinant vaccine designed to control teladorsagiosis in sheepSimon BabayanBiotechnology and Biological Sciences Research Council (BBSRC)BB/M012956/1RI BIODIVERSITY ANIMAL HEALTH & COMPMED