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Investigating the role of the SNARE-associated protein Snapin in human THP-1 macrophage immune response during M. tuberculosis infection
Thesis (MSc)--Stellenbosch University, 2022.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2022
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| _version_ | 1867613733902090240 |
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| access_status_str | Open Access |
| author | Brown, Nicole Karen |
| author2 | Kinnear, Craig John |
| author_browse | Brown, Nicole Karen Kinnear, Craig John |
| author_facet | Kinnear, Craig John Brown, Nicole Karen |
| author_sort | Brown, Nicole Karen |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc)--Stellenbosch University, 2022. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/125013 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:40:50.669Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/125013 Investigating the role of the SNARE-associated protein Snapin in human THP-1 macrophage immune response during M. tuberculosis infection Brown, Nicole Karen Kinnear, Craig John Loos, Ben Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Molecular Biology and Human Genetics. Mycobacterium tuberculosis -- Etiology Immune response -- Molecular aspects Macrophages Autophagy UCTD Thesis (MSc)--Stellenbosch University, 2022. ENGLISH ABSTRACT: Tuberculosis (TB) is a deadly infectious disease that kills millions of individuals each year. The etiological agent of TB, Mycobacterium tuberculosis (M. tuberculosis), is one of the most successful pathogens in terms of survival within the human host. Autophagy is an important degradative process involved in the clearance of M. tuberculosis during infection. However, M. tuberculosis has evolved various mechanisms that disrupt autophagy, allowing it to escape degradation and survive intracellularly. The exact molecular mechanisms underlying these abilities remain to be elucidated. The SNARE-associated protein (Snapin) is known to be involved in autophagy by playing a role in macrophage lysosomal and autophagosomal maturation, however its role in the context of mycobacterial infection remains unknown. This study investigated the role of Snapin in host macrophage response to infection with the M. tuberculosis H37Rv strain, as well as its importance in intracellular mycobacterial survival. The expression of Snapin was quantified in both uninfected and infected human THP-1-derived macrophages at varying time points. The forced reduction of Snapin was achieved via siRNA transfection, after which the intracellular bacterial burden was determined. Here, we present evidence that hints at Snapin’s involvement in host macrophage response to M. tuberculosis infection. More specifically, results indicate elevated Snapin expression and reduced LAMP1 expression in infected macrophages. In Snapin knock-down macrophages, decreased LAMP1 expression and decreased intracellular survival of M. tuberculosis at 48 hours post-infection was observed, which is contradictory to our hypothesis. This suggests that Snapin has a possible role to play in the intracellular survival of M. tuberculosis at 48 hours post-infection, potentially due to its role in autophagy induction. Our findings provide insight into the potential role of Snapin during M. tuberculosis infection and further contribute to the understanding of the molecular mechanisms/components involved during M. tuberculosis infection. AFRIKAANSE OPSOMMING: Tuberkulose (TB) is ʼn dodelike oordraagbare siekte waarvan miljoene mense elke jaar beskyk. Mycobaterium tuberculosis (M. tuberculosis), die organisme vat TB veroorsaak, is een van die mees suksesvolle patogene in terme van oorlewing in mens selle. Outofagie is ʼn belangrike afbrekende proses wat ʼn rol speel in de verwydering van M. tuberculosis gedeurende infeksie. M. tuberculosis het egter verskeie meganismes ontwikkel wat outofagie ontwrig en sodoende vermy dit die afbrekende prosesse en is dus in staat om in die sel te oorleef. Die presiese molekulêre meganisme wat hierdie vermoëns moontlik maak is nog nie ten volle toegelig nie. Die SNARE-geassosieerde proteïen (Snapin) is bekend as ʼn proteinwat ʼn rol speel gedeurnede makrofaag lisosoom en outofagosoom rypwording, maar sy rol in mikobakterium infeksie is steeds onbekend. In hierdie studie word die rol van Snapin in M. tuberculosis H37Rv-infekteerde makrofage en sy rol in intrasellulêre oorlewing van M. tuberculosis bestudeer. Die uitdrukking van Snapin was in geïnfekteerde en ongeïnfekteerde mens THP-1-afgeleide makrofage by verskillende tydpunte bepaal. SiRNA was gebruik om die uitdrukking van Snapin te verlaag eb daarna was die intrasellulêre bakteriële las bepaal. Hier verskaf ons bewyse dat Snapin ʼn rol mag speel in die makrofaag se respons tot M. tuberculosis infeksie. Die resultate van hierdie studie wys dat die vlakke van Snapin verhoog is en dat die vlakke van LAMP1 verlaag is in geïnfekteerde macrofage. Teen 48-uur, in selle waarin die uitdrukking van Snapin verlaag was, was die uitdrukking van LAMP1 asook die intrasellulêre oorlewing van M. tuberculosis oor verlaag. Dit is in teenstryd met ons hipotese. Die resultate stel voor dat 48-uur na infeksie speel Snapin ʼn rol in intrasellulêre oorlewing van M. tuberculosis, moontlik as gevolg van sy rol in die induksie van outofagie. Die bevindinge van hierdie studie gee insig oor die moontlike rol van Snapin gedeurende M. tuberculosis infeksie speel en dra verder by tot die kennis van die molekulêre meganismes wat daarby betrokke is. Masters 2022-02-17T10:37:01Z 2022-04-29T12:50:21Z 2023-03-18T03:00:07Z 2022-02 Thesis http://hdl.handle.net/10019.1/125013 en_ZA Stellenbosch University xi, 78 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Mycobacterium tuberculosis -- Etiology Immune response -- Molecular aspects Macrophages Autophagy UCTD Brown, Nicole Karen Investigating the role of the SNARE-associated protein Snapin in human THP-1 macrophage immune response during M. tuberculosis infection |
| title | Investigating the role of the SNARE-associated protein Snapin in human THP-1 macrophage immune response during M. tuberculosis infection |
| title_full | Investigating the role of the SNARE-associated protein Snapin in human THP-1 macrophage immune response during M. tuberculosis infection |
| title_fullStr | Investigating the role of the SNARE-associated protein Snapin in human THP-1 macrophage immune response during M. tuberculosis infection |
| title_full_unstemmed | Investigating the role of the SNARE-associated protein Snapin in human THP-1 macrophage immune response during M. tuberculosis infection |
| title_short | Investigating the role of the SNARE-associated protein Snapin in human THP-1 macrophage immune response during M. tuberculosis infection |
| title_sort | investigating the role of the snare associated protein snapin in human thp 1 macrophage immune response during m tuberculosis infection |
| topic | Mycobacterium tuberculosis -- Etiology Immune response -- Molecular aspects Macrophages Autophagy UCTD |
| url | http://hdl.handle.net/10019.1/125013 |
| work_keys_str_mv | AT brownnicolekaren investigatingtheroleofthesnareassociatedproteinsnapininhumanthp1macrophageimmuneresponseduringmtuberculosisinfection |