Pulmonary immunomaturation in the neonatal horse: Age-related changes in the pulmonary cytokine milieu and circulating antigen-antibody complexes and their influence on macrophage phenotype and function
Date of Award
Doctor of Philosophy
Veterinary Microbiology and Preventive Medicine
Brett A. Sponseller
The prevalence of neonatal pneumonia exemplifies an age-related immune susceptibility among several mammalian species. The cause of this age-related susceptibility is primarily due to different mechanisms of immune defense within the neonate as compared to the adult. In horses, neonatal foals less than six months of age succumb to pneumonia caused by the intracellular, macrophage-tropic organism, Rhodococcus equi. Fulminant pneumonia in foals caused by R. equi develops as a slow progression of pyogranulomatous pneumonia and causes significant morbidity and mortality on equine breeding farms in horses aged two to six months.
Several studies within the literature provide explanations for this age related-susceptibility including a delayed production of a comprehensive array of endogenous antibody, altered cell-mediated immune responses, and diminished cytokine production by T cells; however, several gaps remain with respect to pulmonary specific immune changes within the ageing foal. The research reviewed in this dissertation focuses on the innate pulmonary cytokine milieu as well as the pulmonary alveolar macrophage (PAM) phenotype and function and how these immune environments and macrophage functions changed during the first year of life in a foal.
Bronchoalveolar lavage fluid (BALF) was collected from a cohort of foals during the first year of life and analyzed during a longitudinal study investigating the pulmonary cytokine milieu and the PAM phenotype and function. Increased concentrations of interleukin-4 (IL-4) within the BALF of neonatal foals early in life and consistent concentrations of tumor necrosis factor-alpha (TNF-α) within the first year of life were discovered. Interestingly, IL-4 concentrations increased within the first two months of life and were virtually undetectable by six months of age. Furthermore, ex vivo PAM were discovered to demonstrate an increased susceptibility to in vitro intracellular infection with R. equi despite applied stimulus.
The final concept investigated, regarding the age-related susceptibility to pneumonia within neonatal horses, included measurement of naturally occurring circulating antigen-antibody complex concentrations. These immune complexes were studied as an alternative mechanism for macrophage activation ultimately resulting in enhanced intracellular microbicidal killing. Importantly, neonatal foals exhibited significantly lower concentrations of circulating immune complexes than adults providing additional evidence to support the notion that macrophages from foals are less capable of adopting a microbicidal phenotype.
Sarah Anne Wiechert-Brown
Wiechert-Brown, Sarah Anne, "Pulmonary immunomaturation in the neonatal horse: Age-related changes in the pulmonary cytokine milieu and circulating antigen-antibody complexes and their influence on macrophage phenotype and function" (2019). Graduate Theses and Dissertations. 17610.