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Doctoral Degrees (Medicine)

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Browsing Doctoral Degrees (Medicine) by Author "Archary, Derseree."

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    Inflammation and cellular immune phenotypes in TB/HIV co-infection = Ukuvuvukala nezinswebu zamasosha omzimba ezinhlayiya ku-TB/HIV.
    (2023) Maseko, Thando Glory.; Sivro, Aida.; Archary, Derseree.
    South Africa has the highest burdens of TB and HIV. HIV induced inflammatory and immune changes are known to increase the risk of TB recurrence and lead to poor disease outcome in co-infected patients. Here we characterised soluble inflammatory, NK and CD4+ T cell profiles in TB and TB/HIV disease. We utilized peripheral blood specimens from the CAPRISA 011 IMPRESS study to characterize NK and memory CD4+ T helper cell phenotypes during active TB and post TB treatment in individuals with or without HIV co infection. We also characterized the effects of these phenotypes on mycobacterial clearance and TB disease severity measured by the presence of lung cavitation. We additionally characterised plasma cytokine/chemokine markers of cavitary disease in drug-resistant TB patients from the CAPRISA 020 InDEX study. TB/HIV co infection led to the expansion of functionally impaired CD56neg NK cell subset. TB treatment completion resulted in restoration of total NK cells, NK cell subset redistribution and downregulation of several NK cell activating and inhibitory receptors. Higher percentage of peripheral CD56bright cells was associated with longer time to culture conversion, while higher expression of NKp46 on CD56dim NK cells was associated with lower odds of lung cavitation in the overall cohort and the TB/HIV co infected participants. With regards to memory CD4+ T cell responses, TB/HIV co infection led to higher percentage of Th2 cells, α4β1 and α4β7 integrin expressing memory CD4+ T cells, and lower percentage of Th9 cells. Increased IL-6 expression during MDR/XDR-TB was associated with higher risk of lung cavitation in CAPRISA 020 participants. Additionally smoking and previous history of TB were associated with increased risk of cavitary disease while HIV and higher BMI were associated with reduced risk of cavitation during MDR/XDR TB. We identified distinct changes in systemic inflammatory and NK cell and memory CD4+ T cell populations with respect to active disease, treatment completion, bacterial clearance and disease severity in TB and TB-HIV co-infected individuals. These results highlight biologically plausible and novel mechanisms by which concurrent HIV infection impairs the host immune control of Mtb infection. Iqoqa. INingizimu Afrikha inomthwalo omkhulu we-TB ne-HIV. I-HIV ifike nokuvuvukala nezinguquko kumasosha omzimba okwaziwa njengokukhulisa ubungozi bokubuya kwe-TB okuholela emiphumeleni emibi yesifo ezigulini eziphethwe nangezinye izifo. Lapha sibona ukuvuvukala okuncibikalayo, i-NK ne-CD4+ ubunjalo bezinhlayiya zika-T ezifweni ze-TB ne-HIV. Sasebenzisa izimelabunjalo zegazi ezingasekugcineni ocwaningweni lwe-CAPRISA 011 IMPRESS ukuze kubonakale i-NK nememori ye-CD4+ yenswebu yenhlayiya engumsizi ka-T ngesikhathi i-TB isenamandla nangemuva kokwelashelwa i-TB kulowo osuke enayo noma engenayo i-HIV nezinye izifo. Sichaza nomthelela wezinswebu zokucaciswa kwemycobacterial nokwenzeka ngamandla kwesifo se-TB okulinganiswa ngobukhona bezimbobo emaphashini. Sibuye sichaze ngabakhombisi besifo sezimbombo zesifo seplasma cytokine/chemokine ezigulini ezimelana nekhambi le-TB ocwaningweni lwe-CAPRISA 020 InDEX. Izifo ezingosomathuba ze-TB/HIV ziholela ekukhuleni kokuphazamiseka kokusebenza kwesethi encane yenhlayiya ye-CD56neg NK. Ukuqedelwa ukwelashelwa i-TB kuholela ekwenziweni kabusha kwezinhlayiya ze-NK, ukusabalaliswa kabusha kwesethi encane ye-NK kanye nokulawulwa maphansi kwezinhlayiya eziningi ze-NK ezenza izamukeli zisebenze noma ziphazamiseke. Iphesenti eliphezulu lezinhlayiya ze-CD56bright zazihlobaniswa nesikhathi eside sokubonakala kwenguquko, ngenkathi izinga eliphezulu lokuziveza kwezinhlayiya ze-NKp46 ku-CD56dim NK kwakuhlobaniswa nezinga eliphansi lokubhoboka kwamaphaphu eqoqweni lonke labantu beminyaka elinganayo kanye nababambiqhaza abane-TB/HIV kodwa bebenezinye izifo ezibaphethe. Ngokwezimpendulo zenhlayiya yememori ye-CD4+ T, izifo mixhantela ye-TB/HIV kwaholela ephesentini eliphezulu lezinhlayiya ze-Th2, i-α4β1 ne-α4β7 i-integrin ikhombisa izinhlayiya zememori ye-CD4+ T nephesenti eliphansi lezinhlayiya ze-Th9. Ukukhula kokuziveza kwe- IL-6 ngesikhathi i-MDR/XDR-TB ihlobaniswa nobungozi bezinga eliphezulu bokubhoboka kwamaphaphu kubabambiqhaza be-CAPRISA 020. Ngaphezu kwalokho ukubhema nomlando owedlule we-TB wahlobaniswa nokukhula kobungcuphe kwesifo sezimbobo emaphashini ngenkathi i-HIV ne-BMI ephezulu kwahlobaniswa nokwehla kobungcuphe bezimbobo emaphashini ngesikhathi se- MDR/XDR TB. Sathola izinguquko ezibonakalayo zabasengcupheni ohlelweni lokuvuvukala, izinhlayiya ze-NK kanye nezinhlayiya ze-CD4+ T ngokwesifo esimandla, ukuqedelwa kokwelashwa, ukuqedwa kwegciwane nokuba mandla kwesifo se-TB ne-HIV kulowo onezinye izifo ezimphethe. Imiphumela yagqamisa iqiniso elikholekayo nendlela yokwelapha okuyiyona okubuye kube nokutheleleka nge-HIV ngesikhathi esisodwa okuyikhona okuphazamisa umgcinikulawulwa kwamasosha omzimba esifo seMtb.