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

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.

SUBMITTER: Babayan SA

PROVIDER: S-EPMC5830876 | biostudies-other | 2018 Feb

REPOSITORIES: biostudies-other

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

Babayan Simon A SA Sinclair Amy A Duprez Jessica S JS Selman Colin C

Scientific reports 20180228 1

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 ...[more]

PMID: 29491449

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Project description:BackgroundQuantifying the burden of parasitic diseases in relation to other diseases and injuries requires reliable estimates of prevalence for each disease and an analytic framework within which to estimate attributable morbidity and mortality. Here we use data included in the Global Atlas of Helminth Infection to derive new global estimates of numbers infected with intestinal nematodes (soil-transmitted helminths, STH: Ascaris lumbricoides, Trichuris trichiura and the hookworms) and use disability-adjusted life years (DALYs) to estimate disease burden.MethodsPrevalence data for 6,091 locations in 118 countries were sourced and used to estimate age-stratified mean prevalence for sub-national administrative units via a combination of model-based geostatistics (for sub-Saharan Africa) and empirical approaches (for all other regions). Geographical variation in infection prevalence within these units was approximated using modelled logit-normal distributions, and numbers of individuals with infection intensities above given thresholds estimated for each species using negative binomial distributions and age-specific worm/egg burden thresholds. Finally, age-stratified prevalence estimates for each level of infection intensity were incorporated into the Global Burden of Disease Study 2010 analytic framework to estimate the global burden of morbidity and mortality associated with each STH infection.ResultsGlobally, an estimated 438.9 million people (95% Credible Interval (CI), 406.3 - 480.2 million) were infected with hookworm in 2010, 819.0 million (95% CI, 771.7 - 891.6 million) with A. lumbricoides and 464.6 million (95% CI, 429.6 - 508.0 million) with T. trichiura. Of the 4.98 million years lived with disability (YLDs) attributable to STH, 65% were attributable to hookworm, 22% to A. lumbricoides and the remaining 13% to T. trichiura. The vast majority of STH infections (67%) and YLDs (68%) occurred in Asia. When considering YLDs relative to total populations at risk however, the burden distribution varied more considerably within major global regions than between them.ConclusionImprovements in the cartography of helminth infection, combined with mathematical modelling approaches, have resulted in the most comprehensive contemporary estimates for the public health burden of STH. These numbers form an important benchmark upon which to evaluate future scale-up of major control efforts.

Dataset Information

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

Publications

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

Similar Datasets

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