The immune response of the goldfish (Carassius auratus L.) to natural mycobacterial pathogens

• Author / Creator

  Hodgkinson, Jordan

• Disease caused by pathogens of the genus Mycobacterium is of serious consequence to many animals, not least of which is M. tuberculosis, the etiological agent of tuberculosis. The ongoing efforts to characterize the immune response during mycobacterial infection have rendered a complex yet incomplete version of events, although molecules, cells, and effector functions central to antimycobacterial immunity have been highlighted through investigation. The ability of mycobacterial pathogens to evade and persist within host phagocytes, co-opt and benefit from granuloma formation, and remain dormant in the majority of immunocompetent individuals is a serious health concern, where an estimated one third of the world’s population is infected by M. tuberculosis. Recently, the use of non-traditional models to study host defense mechanisms, including work in teleosts, has provided new insights into this area of research.
  My doctoral research focused on the immune response of goldfish to natural mycobacterial pathogens, M. marinum, M. chelonae and M. fortuitum, utilizing these infection models that vary in overall pathogenicity. I characterized the cytokine-induced alternative functional phenotype of primary goldfish macrophages and the relative antimicrobial states of effector phagocytes in response to pathogenic challenge. I measured the expression of cytokines that are central to the control of mycobacterial immunity in higher vertebrates in goldfish infected with each pathogen. This graded level of host protection and bacterial load allowed for the assessment of each immune parameter and the corollary infection outcome.
  Similar to mammals, goldish macrophages are broadly capable of polarization into classically (M1) and alternatively (M2) activated macrophages. I characterized the cytokine-driven polarization of goldfish primary kidney macrophages into an M2 phenotype, marked by the increase in arginase activity and the corresponding dampening of nitric oxide production. I utilized the established effector functions for primary kidney leukocytes to detail them in response to exposure to natural mycobacterial pathogens. M. marinum demonstrated the capacity to evade nitric oxide production and promoted arginase activity. Moreover, a varying capacity of neutrophils to respond to each pathogen was observed, with generally less responsiveness to M. marinum. Additionally, growth and bacteremia of M. marinum in goldfish spleen and kidney increased through the first 4 weeks of infection, while bacteremia of M. chelonae and M. fortuitum diminished at every observable time point. Together, these findings suggest mycobacterial evasion strategies that contribute to a less effective immune response to M. marinum. 

• Subjects / Keywords

  • macrophage
  • mycobacteria
  • comparative immunology

• Graduation date

  Fall 2018

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3TH8C37S

• License

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