Understanding the interaction between mycoplasma bovis and bovine respiratory macrophages
Date
2019-05-14
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Thesis
Degree Level
Doctoral
Abstract
Mycoplasma bovis is the most pathogenic bovine mycoplasma in Europe and North America. It forms an important component in bovine respiratory disease (BRD) complex, a multifactorial disease of feedlot cattle that causes major economic loss. Natural occurring M. bovis persist in a herd over an extended period and can be consistently identified not only in lesions but also commonly in healthy lungs and those with pneumonia indicating that M. bovis is capable of persisting in lungs of recovered animals. This suggests that M. bovis can modulate alveolar macrophage effector functions, although the mechanisms employed by M. bovis are not well understood. In this thesis, I determined how M. bovis modulates bovine alveolar macrophage (BAM) effector functions. I used primary alveolar macrophages infected with M. bovis Mb1 to demonstrate that the production of nitric oxide and cytokines was impaired. I observed a significant reduction in the production of nitric oxide and the pro-inflammatory cytokine TNF-α coupled with a decrease in gene transcription of iNOS, the nitric oxide synthase gene and an increase of IL-10 expression in infected BAMs. These results suggest modulation of the immune response by M. bovis. To better understand other strategies of immune suppression by M. bovis to evade the host immune responses, I focused on the ability of M. bovis to modulate macrophage apoptosis during infection. Previously, studies on M. bovis infection have reported it to exert both pro- and anti-apoptotic effects on a diversity of cell types, including neutrophils, lymphocytes, monocytes and macrophages. In this thesis, I sought to understand the mechanism of inhibition of apoptosis using a BoMac bovine macrophage cell line to identify the apoptosis pathways modulated by M. bovis infection. Our findings suggest novel mechanisms that M. bovis strain Mb1 delays STS-induced apoptosis via the intrinsic pathway in a caspase dependent manner by inhibition of caspases 3, 6, and 9; decreased cytochrome c release; activation of NF-β with anti-apoptotic consequences of increased up-regulation of the anti-apoptotic survival genes Bcl-XL and Bcl-2 and absence of DNA fragmentation. These results support the observation that M. bovis inhibit apoptosis for survival and potentially facilitate bacterial survival, replication and transmission. Understanding the factors that contribute to virulence, dissemination and immune evasion of a pathogen is critical knowledge to contemplating new vaccines and therapeutics.
Description
Keywords
Mycoplasma bovis, Alveolar macrophage, Apoptosis
Citation
Degree
Doctor of Philosophy (Ph.D.)
Department
Veterinary Microbiology
Program
Veterinary Microbiology