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A Proteomic and Transcriptomic Evaluation of Extracellular Vesicles From Larval Excretory-Secretory Products of Toxocara canis and Toxocara cati
A Proteomic and Transcriptomic Evaluation of Extracellular Vesicles From Larval Excretory-Secretory Products of Toxocara canis and Toxocara cati
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151923
- ISBN
- 9798384048527
- DDC
- 636
- 서명/저자
- A Proteomic and Transcriptomic Evaluation of Extracellular Vesicles From Larval Excretory-Secretory Products of Toxocara canis and Toxocara cati
- 발행사항
- [Sl] : Cornell University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 242 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
- 주기사항
- Includes supplementary digital materials.
- 주기사항
- Advisor: Bowman, Dwight.
- 학위논문주기
- Thesis (Ph.D.)--Cornell University, 2024.
- 초록/해제
- 요약Derived from the Latin meaning "one who eats with another," parasites have been an ever-present menace to their hosts, adapting and co-evolving with them over the years in order to survive within the host body and reap the many benefits of this lifestyle, be it acquisition of host nutrients, protection from the outside environment, or dispersion of future generations across a broader geographic area. Parasites have evolved to induce inflammation and subsequent breakdown of host barriers, yet have also developed tactics to avoid clearance by the host immune system, and withstand the onslaught of attack from host immune cells. Such immunomodulatory strategies have awarded parasites incredible success, with parasites described for thousands of different host species, whether mammal, reptile, fish, bird, or human, and distribution across all continents.One such parasite genus, Toxocara, is particularly well adapted towards survival within its host. Indeed, past reports have described parasitic larvae capable of surviving for up to a decade unchanged within one experimentally infected host. Toxocara canis and Toxocara cati, which reside in canid and felid definitive hosts, respectively, are capable of infecting a variety of paratenic hosts, in which they survive without development to the next life stage, as well as accidental or aberrant hosts, such as humans, where they can result in a variety of clinical signs following migration throughout the body. Due to the disease caused by these parasites in both animals and humans, it is of the utmost importance to further study the immunomodulatory strategies employed by these nematodes.First, I present an overview of the lifecycle and biology of Toxocara canis and Toxocara cati, discussing the disease caused in dogs and cats, as well as diagnosis and treatment strategies, and detailing previous experiments analyzing the larval migration routes through paratenic hosts and human aberrant hosts. Next, I review parasite immunomodulatory mechanisms, first framing this understanding from a historical perspective, then discussing the host immune system response before ultimately describing parasitic methods that counteract this response.I then describe the experiments performed in order to better understand the immunomodulatory mechanisms at play with toxocariasis, focusing on the more recently described extracellular vesicles (EVs), which contain a variety of cargo molecules, and are capable of trans-phylum cellular interaction. I first evaluated many published methods of EV isolation, testing the efficiency and usability of each method as it pertains to the isolation of highly concentrated and purified EV samples from larval flasks of T. canis and T. cati.I follow this discussion with an analysis of the protein cargo within isolated EVs, comparing this with the freely-secreted protein fraction, and describe several immunomodulatory proteins identified through these proteomic analyses. Next, I describe the RNA analysis results, where sequencing of small RNAs within the EV cargo revealed many miRNAs, some of which also have immunomodulatory properties described. Lastly, I describe the results of differential expression experiments performed on mouse cells with known immune functions, detailing the many significantly upregulated and downregulated genes in cells exposed to EVs.I conclude by discussing some of the limitations of these experiments, how these could be addressed in future studies, and the more broad applications of this work as it relates to improvement in diagnostic methods, treatments, and potential generation of novel therapeutic interventions. While many questions remain in regards to the intricate and complex methods of immunomodulation following Toxocara spp. infection, these studies contribute new and valuable information towards this understanding, and build a foundation upon which to further research and examine these parasites.
- 일반주제명
- Animal sciences
- 일반주제명
- Parasitology
- 일반주제명
- Immunology
- 키워드
- Helminths
- 키워드
- Parasite
- 키워드
- Toxocara canis
- 키워드
- Toxocara cati
- 기타저자
- Cornell University Animal Science
- 기본자료저록
- Dissertations Abstracts International. 86-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211151923
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■020 ▼a9798384048527
■035 ▼a(MiAaPQ)AAI31300358
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a636
■1001 ▼aWu, Timothy Kevin.▼0(orcid)0000-0003-0515-4079
■24512▼aA Proteomic and Transcriptomic Evaluation of Extracellular Vesicles From Larval Excretory-Secretory Products of Toxocara canis and Toxocara cati
■260 ▼a[Sl]▼bCornell University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a242 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-03, Section: B.
■500 ▼aIncludes supplementary digital materials.
■500 ▼aAdvisor: Bowman, Dwight.
■5021 ▼aThesis (Ph.D.)--Cornell University, 2024.
■520 ▼aDerived from the Latin meaning "one who eats with another," parasites have been an ever-present menace to their hosts, adapting and co-evolving with them over the years in order to survive within the host body and reap the many benefits of this lifestyle, be it acquisition of host nutrients, protection from the outside environment, or dispersion of future generations across a broader geographic area. Parasites have evolved to induce inflammation and subsequent breakdown of host barriers, yet have also developed tactics to avoid clearance by the host immune system, and withstand the onslaught of attack from host immune cells. Such immunomodulatory strategies have awarded parasites incredible success, with parasites described for thousands of different host species, whether mammal, reptile, fish, bird, or human, and distribution across all continents.One such parasite genus, Toxocara, is particularly well adapted towards survival within its host. Indeed, past reports have described parasitic larvae capable of surviving for up to a decade unchanged within one experimentally infected host. Toxocara canis and Toxocara cati, which reside in canid and felid definitive hosts, respectively, are capable of infecting a variety of paratenic hosts, in which they survive without development to the next life stage, as well as accidental or aberrant hosts, such as humans, where they can result in a variety of clinical signs following migration throughout the body. Due to the disease caused by these parasites in both animals and humans, it is of the utmost importance to further study the immunomodulatory strategies employed by these nematodes.First, I present an overview of the lifecycle and biology of Toxocara canis and Toxocara cati, discussing the disease caused in dogs and cats, as well as diagnosis and treatment strategies, and detailing previous experiments analyzing the larval migration routes through paratenic hosts and human aberrant hosts. Next, I review parasite immunomodulatory mechanisms, first framing this understanding from a historical perspective, then discussing the host immune system response before ultimately describing parasitic methods that counteract this response.I then describe the experiments performed in order to better understand the immunomodulatory mechanisms at play with toxocariasis, focusing on the more recently described extracellular vesicles (EVs), which contain a variety of cargo molecules, and are capable of trans-phylum cellular interaction. I first evaluated many published methods of EV isolation, testing the efficiency and usability of each method as it pertains to the isolation of highly concentrated and purified EV samples from larval flasks of T. canis and T. cati.I follow this discussion with an analysis of the protein cargo within isolated EVs, comparing this with the freely-secreted protein fraction, and describe several immunomodulatory proteins identified through these proteomic analyses. Next, I describe the RNA analysis results, where sequencing of small RNAs within the EV cargo revealed many miRNAs, some of which also have immunomodulatory properties described. Lastly, I describe the results of differential expression experiments performed on mouse cells with known immune functions, detailing the many significantly upregulated and downregulated genes in cells exposed to EVs.I conclude by discussing some of the limitations of these experiments, how these could be addressed in future studies, and the more broad applications of this work as it relates to improvement in diagnostic methods, treatments, and potential generation of novel therapeutic interventions. While many questions remain in regards to the intricate and complex methods of immunomodulation following Toxocara spp. infection, these studies contribute new and valuable information towards this understanding, and build a foundation upon which to further research and examine these parasites.
■590 ▼aSchool code: 0058.
■650 4▼aAnimal sciences
■650 4▼aParasitology
■650 4▼aImmunology
■653 ▼aAscaridoid nematodes
■653 ▼aHelminths
■653 ▼aParasite
■653 ▼aToxocara canis
■653 ▼aToxocara cati
■690 ▼a0475
■690 ▼a0718
■690 ▼a0982
■71020▼aCornell University▼bAnimal Science.
■7730 ▼tDissertations Abstracts International▼g86-03B.
■790 ▼a0058
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17162140▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
