Can Infectious Disease Control Be Achieved without Antibiotics by Exploiting Mechanisms of Disease Tolerance?

Lopez, Brina S.

doi:10.4049/immunohorizons.2200043

Cited by 5 publications

(1 citation statement)

References 107 publications

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“…In spite of the biosecurity strategies and partly due to current systems themselves, the incidence of multifactorial production diseases is persistently high, and this is considered as a sign that the farm animals' ability to adapt to the demanding circumstances and high production output is overstressed (Opriessnig et al, 2011;Sundrum, 2015;Wisnieski et al, 2019). This strongly suggests that important issues that affect the development of diseases are ignored and that additional strategies are required to cope with livestock diseases (Hassan et al, 2022;Knaus, 2009;Lopez, 2022;Nakov et al, 2019;Proudfoot & Habing, 2015;Sundrum, 2015). As the most important issue, it is suggested that little attention has been paid to the animal's capacity to cope with disturbances and that allow them to bounce back to normal functioning after disturbances (Nakov et al, 2019; Saborido & Moreno, 2015; Scheffer et al, 2018).…”

Section: The Relevance Of Animal Resilience In Relation To Diseasesmentioning

confidence: 99%

Disease resilience in farm animals

van Dixhoorn

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To diminish the detrimental impact of diseases and to improve farm animal health, it has been suggested to enhance disease resilience of the animals. Good disease resilience can be described as the ability of animals to be minimally affected by challenges that can cause disease and, if affected, to recover quickly. At this moment, knowledge is limited on how to operationalise disease resilience into farm management, in favour of animal health. Knowledge is required whether disease resilience can be influenced and even predicted, so we know how animals will respond to disease challenges they may encounter. The aim of this thesis was to investigate potential influencing factors and possible predictive indicators of resilience to typical multifactorial production related diseases in livestock animals. Disease resilience was quantified in pigs by measuring the duration, recovery and severity of the symptoms after a challenge with a respiratory co-infection model of Porcine Respiratory Reproductive and Respiratory Syndrome Virus (PRRSV) and Actinobacillus pleuropneumoniae (A. pleuropneumoniae). The effect of housing condition on disease resilience was studied by the introduction of social and environmental enrichment to one study group in comparison to the resilience of pigs that were conventionally housed. The application of enrichment benefitted resilience of pigs to the coinfection, by an accelerated viral clearance and a reduction of the risk and severity of lung lesions. In dairy cows the calving was seen as challenge and the period after transition of the dry to the lactation phase was used to monitor various clinical deviations as proxies of resilience, because this is the time when cows become most susceptible to diseases. To test whether (dynamic aspects of) variables could predict disease outcome, a number of physiological, immunological and behavioural variables were measured in pigs and cows prior to the challenges and tested as (dynamic) indicators of resilience ((D)IORs). The indicators of resilience that were found could consist of single measurements, the average values of multiple measurements (IORs), or the dynamic features of continuous measurements (DIORs). In pigs a higher level of lymphocytes, naïve T helper cells, memory T cells and higher relative levels of granulocytes and raised concentrations of natural (auto-) antibodies (N(A)Abs) were found as predicting IORs for the severity of the co-infection. In dairy cows, high average of eating time, high variance in ear temperature and strict regularity in behaviour including rumination and activity, were found as (D)IORs for duration and severity of post-partum diseases, summarised as a Total Deficit Score. This thesis shows that disease resilience of animals improves when they are kept under conditions that better meet their needs. Subsequently, indicators were found that can predict how animals will respond to disease challenges. These (D)IORs provide insight in the disease resilience upon perturbations. As a consequence, the influencing factors ...

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Section: The Relevance Of Animal Resilience In Relation To Diseasesmentioning

confidence: 99%

Disease resilience in farm animals

van Dixhoorn

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Negative immune regulation contributes to disease tolerance in Drosophila

Prakash

Monteith

Vale

2021

Preprint

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Disease tolerance is an infection phenotype where hosts show relatively high health despite harbouring elevated pathogen loads. Compared to the mechanisms of immune clearance our knowledge of the mechanisms underlying increased tolerance remains incomplete. Variation in the ability to reduce immunopathology may explain why some hosts can tolerate higher pathogen burdens with reduced pathology. Negative immune regulation would therefore appear to be a clear candidate for a mechanism underlying disease tolerance but this has not been tested directly for bacterial infections. Here, we examined how the negative regulation of the immune deficiency (IMD) pathway affects disease tolerance in Drosophila melanogaster when infected with the gram-negative bacterial pathogen Pseudomonas entomophila. We find that UASRNAi-mediated reduced expression of the negative regulators of IMD (pirk & caudal) severely reduced the ability to tolerate infection in both males and females across a wide range of infectious doses. While flies unable to regulate the IMD response exhibited higher expression of antimicrobial peptides and lower bacterial loads as expected, this was not accompanied by a proportional reduction in mortality. Instead, tolerance (measured as fly survival relative to its microbe load) was drastically reduced, likely due to the combination of increased immunopathology and cytotoxicity of elevated AMP expression. Our results therefore highlight that in addition to regulating an efficient pathogen clearance response, negative regulators of IMD also contribute to disease tolerance.

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Negative immune regulation contributes to disease tolerance in Drosophila melanogaster

Prakash,

Monteith,

Vale

2024

Physiological Entomology

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Disease tolerance is an infection phenotype where hosts show relatively high health despite harbouring elevated pathogen loads. Variation in the ability to reduce immunopathology may explain why some hosts can tolerate higher pathogen burdens with reduced pathology. Negative immune regulation would therefore appear to be a clear candidate for a mechanism underlying disease tolerance. Here, we examined how the negative regulation of the immune deficiency (IMD) pathway affects disease tolerance in Drosophila melanogaster when infected with four doses of the gram‐negative bacterial pathogen Pseudomonas entomophila. We find that while flies unable to regulate the IMD response exhibited higher expression of antimicrobial peptides and lower bacterial loads as expected, this was not accompanied by a proportional reduction in mortality. Instead, ubiquitous UAS‐RNAi knockdown of negative regulators of IMD (pirk and caudal) substantially increased the per‐pathogen‐mortality in both males and females across all tested infectious doses. Our results therefore highlight that in addition to regulating an efficient pathogen clearance response, negative regulators of IMD also contribute to disease tolerance.

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Can Infectious Disease Control Be Achieved without Antibiotics by Exploiting Mechanisms of Disease Tolerance?

Cited by 5 publications

References 107 publications

Disease resilience in farm animals

Disease resilience in farm animals

Negative immune regulation contributes to disease tolerance in Drosophila

Negative immune regulation contributes to disease tolerance in Drosophila melanogaster

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