University of Illinois Urbana-Champaign

The impact of maternal immune activation on pig muscle development and postnatal immune function

Bryan, Erin Elizabeth

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BRYAN-DISSERTATION-2022.pdf

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https://hdl.handle.net/2142/117808

Description

Title
The impact of maternal immune activation on pig muscle development and postnatal immune function
Author(s)
Bryan, Erin Elizabeth
Issue Date
2022-12-02
Director of Research (if dissertation) or Advisor (if thesis)
Dilger, Anna C
Doctoral Committee Chair(s)
Dilger, Ryan N
Committee Member(s)
  • Steelman, Andrew J
  • Beever, Jonathon E
Department of Study
Animal Sciences
Discipline
Animal Sciences
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
  • immune
  • isoflavone
  • myogenesis
  • inflammation
  • fetal programming
Abstract
Gestational environment influences fetal development, resulting in differential postnatal performance. External signals, such as maternal circulating inflammatory cytokines or pathogens, can program the offspring in ways counterproductive to efficient postnatal growth. In particular, inflammatory cytokines are antagonistic to myogenesis, thereby stunting the animal’s growth potential. Further, there is some evidence that maternal immune activation alters the fetal immune system, thereby determining the efficiency with which the offspring will overcome postnatal pathogens. Inflammatory stimuli are ubiquitous in swine production, even in high health herds. Despite this, little is known about the effect of maternal immune activation on pig development and subsequent postnatal performance. Therefore, the overall objective of this work was to determine the impact of maternal inflammation during mid-gestation on pig muscle development and postnatal immune response. Two total experiements were conducted for this work. In the first study, thirteen first-parity gilts (“gilts”) were randomly allotted into one of three treatments: not infected and fed a diet devoid of isoflavones (CON), infected with porcine reproductive and respiratory syndrome virus (PRRSV) and fed the control diet (POS) or that supplemented with 1,500 mg/kg soy-derived isoflavones (ISF). After farrowing (GD 114 ± 2), 1-2 offspring (“pigs”) closest to the average litter weight were selected either at birth (3 ± 2 d of age) or weaning (21 ±2 d of age) to determine body, muscle, and organ weights as well as muscle cell number and size. Four weaned pigs of average body weight within each litter were selected for postnatal immune challenge. At PND 52, pigs were injected with 5 µg/kg BW lipopolysaccharide (LPS) intraperitoneally. Serum was collected at 0, 4, and 8 h following LPS administration to analyze tumor necrosis factor alpha (TNF-α). At PND 59, pigs were administered a novel vaccine to elicit an adaptive immune response. At PND 59, 66, and 73, peripheral blood mononuclear cells were isolated and T-cell populations determined by flow cytometry. At PND 21, ISF pigs had reduced (P ≤ 0.05) whole body and muscle weights, but greater (P < 0.05) kidney weight compared with CON, and greater (P < 0.05) relative liver weight compared with CON and POS. Muscle fiber number and size were not different (P > 0.39) between groups at birth or weaning. After LPS administration, TNF-α was greatest in ISF pigs (P < 0.05) at both 0 and 8 h post-challenge. At the peak time-point of 4 h post-challenge, ISF pigs had the greatest concentration of TNF-α and CON pigs had the lowest, with POS pigs being intermediate (P = 0.01). After vaccination, ISF offspring had shifts in T-cell populations indicating an impaired immune response. For the second experiment, 30 first-parity gilts were randomly allotted into one of two treatments: repeated intravenous injections with lipopolysaccharide (LPS; n=8, treatment code INFLAM) or a comparable volume of phosphate buffered saline (CON, n=8). Injections began on gestational day (GD) 70 and took place every other day until GD 84. The initial dose was 10 μg LPS/kg BW and was increased 12% at each subsequent dose to prevent the development of endotoxin tolerance. On GD 70, 76, and 84, blood was collected at 0 and 4 h post-injection via jugular or ear venipuncture to determine tumor necrosis factor (TNF) -α, interleukin (IL) -6, and IL-1β concentrations. Although initially designed to be a repeated injection challenge with accelerating doses, many gilts were experienced adverse outcomes (i.e., mortality and abortion) after the initial dose of LPS. This resulted in three experimental groups to determine the underlying causes of adverse outcomes, included CON (n=8), LPS (n=8), and gilts with adverse outcomes (LPS-ADV, n=13). Mortality and abortion rates are reported as number of instances out of the total number of gilts challenged. At 0 h post-injection, TNF-α, IL-6, and IL-1β concentrations did not differ (P ≥ 0.11) among treatments. Additionally, TNF-α, IL-6, and IL-1β concentrations did not differ (P ≥ 0.30) from 0 to 4 h post-injection in CON gilts, the expected result from an injection of saline. However, from 0 to 4 h post-injection, LPS gilts had an approximately 26 fold and 1.5 fold increase (P < 0.01) in TNF-α and IL-6 concentration, respectively. This was the intended outcome of the immune activation model. Comparatively, LPS-ADV gilts had an approximately 206 fold and 2 fold increase (P < 0.01) in TNF-α and IL-6 concentration, respectively. The gilts that completed the injection regimen (LPS) were a part of a larger experiment investigating offspring outcomes. On postnatal d (PND) 3, the pig closest to the litter average was selected for dissection and muscle fiber characterization. On PND 52, the third barrow closest to the litter average was selected for innate immune challenge. Pigs were administered 5 μg LPS/kg BW via intraperitoneal injection, and blood was collected at 0, 4, and 8 h post-injection to determine TNF-α concentration. There were no differences between LPS and CON gilts in litter mortality outcomes (P ≥ 0.13), but LPS pigs were smaller (P = 0.04) at birth and tended (P = 0.09) to be smaller at weaning. Muscle and organ weights did not differ (P ≥ 0.17) between treatments, with the exception of the semitendinosus, which was smaller (P < 0.01) in LPS pigs. LPS pig TNF-α concentration did not differ across time, while CON pig TNF-α concentration peaked (P = 0.01) at 4 h post-injection. Overall, these experiments indicate maternal immune activation did not alter pig muscle development, but resulted in suppressed innate and adaptive immune activation.
Graduation Semester
2022-12
Type of Resource
Thesis
Handle URL
https://hdl.handle.net/2142/117808
Copyright and License Information
Copyright 2022 Erin Bryan

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