Trained innate immunity and transgenerational effects in chickens: A conceptual approach of non-genetic inheritability

Michel Bernardus Verwoolde

Research output: Thesisinternal PhD, WU

Abstract

Within the poultry husbandry sector, the containment of infectious diseases has always been a significant focus area and needs new sustainable and alternative strategies to control and minimize the vulnerability for increased incidences of infectious diseases and related health problems. An important factor within the poultry husbandry sector is the impact of the hens on the well-being and fitness of their offspring. It now becomes clear that immunological transgenerational effects have long lasting effects on the physiology of an organism. Especially the impact of the mother on the next generation via non-genetic manners, and within this, the role of the innate immune system is poorly understood. The innate immune system has the potential to protect chickens against infections in a non-pathogen specific manner, especially at a young age when the adaptive immune system has not yet fully developed and the newly hatched chicks are depending on the innate immune system and maternal antibodies. A mechanism within monocytes and macrophages of the innate immunity has been described, where one innate antigenic stimulus can lead to an amplified response against other unrelated stimuli. This concept is known in mammals as trained innate immunity and is characterized by a crosstalk between immune, epigenetic and metabolic pathways in monocytes, macrophages and NK cells, featuring three core mechanisms, namely: 1) immune adaptations, 2) metabolic reprogramming and 3) epigenetic DNA modifications. The observations of both experiments in chapter 2 suggest a functional link between the maternal innate immune system and the immune system of the offspring. A proposed mechanism for this functional link was trained innate immunity. Chapter 3 describes the development and optimization of a model to study trained innate immunity in vitro in chickens. This model was adapted from studies in mammalian species. Primary blood derived monocytes were stimulated with β-glucan or LPS. Next, the cells were secondary stimulated with LPS and differences in pro-inflammatory responses were analysed as a read-out for trained innate immunity. In addition, possible effects of the cytokines IL-4 and IFNγ on trained innate immunity were investigated to study some molecular and/or cellular pathways in more detail. I observed that after the secondary LPS stimulation, surface expression of colony stimulating factor 1 receptor (CSF1R) and the activation markers CD40 and major histocompatibility complex class II (MHC-II) were higher on macrophages that were trained with a combination of β-glucan and IL-4 compared to unstimulated cells. The positive effects on gene expression were paralleled by enhanced NO production. These results provided the first indications that innate immune training is also present in chicken. In chapter 4, I further compared trained innate immunity of monocytes in different chicken breeds. To this end, I investigated whether isolated primary monocytes from layers and broilers differ in their innate training capacity. I demonstrated again trained innate immunity in chicken but now based on parameters associated with immune function (i.e. IL1-β, MHCII, CD40, iNOS, NO) and metabolism (HIF-1α, PPARγ, lactate). This in vitro study demonstrates that monocytes from different genetic backgrounds can be trained. However, the observed differences suggest a differential effect on immune functionality associated with innate training. Based on analogy with mammalian species I expect a role for epigenetic programming in innate training in chickens. In mammals, the Dectin-1–Akt–mTOR–HIF-1α pathway plays a role in the interplay between epigenetics and metabolism. Interestingly, I found increased HIF-1α gene expression levels in trained macrophages which suggests a role for the Dectin-1–Akt–mTOR–HIF-1α pathway in trained innate immunity of chickens as well. Next, I investigated whether transgenerational effects of maternal activation of innate immunity could influence the response against a pathogenic challenge and performance in broiler chickens (Chapter 5). I investigated whether activation of the innate immune system in broiler breeder hens via β-glucan in the feed and LPS intratracheally had effects on growth performance and immune responsiveness in the neonates. To investigate changes in immune responsiveness and growth performance I used a necrotic enteritis challenge. I showed that maternal stimulation with LPS and β-glucan resulted in decreased gene expression levels of IL-1β in blood-derived monocytes in the offspring. This effect indicated again transgenerational effects of the innate immune system. Next to that, maternal stimulation with LPS resulted in an improved feed efficiency in the offspring in the first week after a necrotic enteritis pathogenic challenge (Chapter 5). The data are a first indication that broiler breeder hens can affect immune responsiveness and feeding efficiency of their offspring in a transgenerational manner. The research of this thesis is the first describing trained innate immunity and non-genetic transgenerational effects of the innate immune system in chickens. I found evidence of the modulating effects of innate immunity in a transgenerational fashion indicating transgenerational trained innate immunity in chicken (Chapter 2, 3, 4 and 5). My overall conclusion is that maternal immune experiences, such as infections or vaccinations, influence the immune system in the offspring. This also influence the effects of dietary interventions with feed additives on the immune system in the offspring. Within this, trained innate immunity has great potentials to be used in adapting current vaccination and feeding strategies to further improve disease resistance, animal performance and animal welfare in the poultry husbandry industry. Knowledge about transgenerational effects of maternal immunization or infection will contribute to a better understanding of the variation in immune phenotypes, disease resistance and metabolic disorders in the next generation(s).

Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
Supervisors/Advisors
  • Kemp, Bas, Promotor
  • Lammers, Aart, Co-promotor
  • Jansen, Christine, Co-promotor
  • van Baal, Jurgen, Co-promotor
Award date4 Jul 2022
Place of PublicationWageningen
Publisher
Print ISBNs9789464472363
DOIs
Publication statusPublished - 2022

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