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Immune Activation Profile in Persons with Latent Tuberculosis Infection

Huaman Joo, Moises
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1637065209854143

Abstract Details

2021, MS, University of Cincinnati, Medicine: Immunology.
Latent tuberculosis infection (LTBI) has been associated with increased cardiovascular disease (CVD) risk. Enhanced systemic T cell and monocyte activation are known drivers of atherosclerotic CVD risk in other infectious and inflammatory conditions, but whether levels of immune activation are augmented in LTBI and thus contribute to CVD risk in LTBI individuals is unclear. We conducted an in-depth profiling of monocyte and T cell subsets in LTBI and non-LTBI subjects. Individuals 40 to 70 years of age were recruited in Lima, Peru. Participants underwent QuantiFERON®-TB testing to define LTBI, completed a coronary computed tomography angiography to assess for coronary artery disease (CAD), and provided peripheral blood for immunologic studies. Luminex and enzyme-linked immunosorbent assays were used to measure soluble markers of immune activation in plasma. We conducted flow cytometry studies for immunophenotyping of monocytes and T cell subsets at baseline and upon ex vivo stimulation with lipopolysaccharide (LPS), PMA/ionomycin, and Mycobacterium tuberculosis (Mtb) antigens (ESAT-6/CFP-10 and Mtb-lysate). A total of 41 LTBI and 28 non-LTBI subjects had stored plasma available for soluble marker analyses. Of these participants, 36 LTBI and 22 non-LTBI subjects had stored peripheral blood mononuclear cells available for complete flow cytometry analyses for this project. Overall, there were no significant differences in baseline clinical characteristics of LTBI and non-LTBI subjects. We found no influence of LTBI in soluble markers of immune activation nor CD38/HLA-DR expression and activation profile of T cell subsets at baseline, but LTBI was associated with higher frequency of HLA-DR+CD38-CD8+ T cells after PMA/ionomycin stimulation. Compared to non-LTBI controls, LTBI individuals exhibited higher density of the CD36 lipid scavenger receptor on total monocytes (median CD36 MFI; 23245 vs. 28826; p=0.017) and intermediate monocytes (median CD36 MFI; 29612 vs. 21826; p=0.006), enhanced density of the chemokine receptor CX3CR1 on non-classical monocytes (median CX3CR1 MFI; 1792 vs. 1610, p=0.047), and increased proportion of non-classical monocytes expressing interleukin-6 (% of IL-6+ cells; 44.9 vs. 26.9, p=0.014) and tumor necrosis factor-? (% of TNF-?+ cells; 62.3 vs. 35.1, p=0.014) upon LPS stimulation. LTBI participants with CAD exhibited a lower density of CD36 expression on total monocytes (median CD36 MFI; 21824 vs. 30567; p=0.003), and higher proportions of ESAT-6/CFP-10-specific IFN-g+CD4+ T cells (% of IFN-g+ cells; 0.18 vs. 0.06; p=0.029), Mtb-lysate-specific IFN-g+ CD4+ T cells (% of IFN-g+ cells; 0.33 vs. 0.21; p=0.022), and Mtb-lysate-specific TNF-a+ CD4+ T cells (% of TNF-a+ cells; 0.77 vs. 0.44; p=0.043), compared to LTBI subjects without CAD. Our results indicate distinct pro-inflammatory alterations of monocyte subsets in LTBI individuals, particularly within the non-classical monocyte subset that showed increased CX3CR1 expression and enhanced pro-inflammatory cytokine production. Presence of CAD correlated with the magnitude of Mtb-specific CD4+ T cell responses, suggesting a pathogen specific contribution to atherosclerotic CVD risk that warrants further investigation.
George Deepe, M.D. (Committee Chair)
Jonathan Katz (Committee Member)
Claire Chougnet, Ph.D. (Committee Member)
49 p.
Immunology
immune activation; inflammation; monocyte; T cell; tuberculosis; cardiovascular disease

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Citations

  • Huaman Joo, M. (2021). Immune Activation Profile in Persons with Latent Tuberculosis Infection [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1637065209854143

    APA Style (7th edition)

  • Huaman Joo, Moises. Immune Activation Profile in Persons with Latent Tuberculosis Infection. 2021. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1637065209854143.

    MLA Style (8th edition)

  • Huaman Joo, Moises. "Immune Activation Profile in Persons with Latent Tuberculosis Infection." Master's thesis, University of Cincinnati, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1637065209854143

    Chicago Manual of Style (17th edition)

ucin1637065209854143
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