Fig 1.
Flow chart of the recruitment and enrollment process of study participants.
ART- naïve newly diagnosed HIV-infected individuals were recruited from the ART clinics of the UoG-CSH, Gondar Health Center, and Maraki Health Center, Gondar, Ethiopia (A). The HIV-negative healthy controls fulfilling the blood donation criteria were recruited from the central Gondar blood bank, Gondar, Ethiopia (B).
Table 1.
Socio-demographic and clinical characteristics of study participants.
Fig 2.
HIV infection significantly reduced the level of Th1 cytokines in LTB-infected and LTB-negative individuals.
The PBMCs isolated from HIV+LTB- (n = 27), HIV+LTB+ (n = 13), HIV-LTB+ (n = 15), and HIV-LTB- (n = 15) were stimulated with media alone (Unstim), PPD or SEB and cultured for 19 hours at 37°C, and the PBMC supernatants were harvested. The levels of IFN-gamma and IL-2 were determined in plasma and from PBMC supernatants using a cytometric bead array. Data were presented using the median with IQR. The cytokine response was compared across the four groups using the Kruskal Wallis test, followed by Dunn’s post hoc multiple comparisons test to compare the median expression level of cytokine in each group. A): level of IFN-gamma production by PBMCs with or without stimulations, B): level of IFN-gamma in plasma, C): level of IL-2 production by PBMCs with or without stimulations, D): level of IL-2 in plasma. Unstim: unstimulated; PPD: purified protein derivative; SEB: staphylococcus enterotoxin B; HIV+LTB-: HIV positive-LTB negative; HIV+LTB+: HIV-LTB co-infected; HIV-LTB+: HIV negative- LTB positive; HIV-LTB-: HIV-negative and LTB-negative. *: p < 0.05, **: p < 0.01, ***: p < 0.001.
Fig 3.
Reduced plasma level of pro-inflammatory cytokines in HIV-LTB co-infected and HIV positive LTB negative individuals.
The PBMCs isolated from HIV+LTB- (n = 27), HIV+LTB+ (n = 13), HIV-LTB+ (n = 15), and HIV-LTB- (n = 15) individuals were stimulated with media alone (Unstim), PPD or SEB and cultured for 19 hours at 37°C, and PBMC supernatants were harvested. The levels of TNF-alpha and IL-6 were determined in plasma and from PBMC supernatants using a cytometric bead array. Data were presented using median with IQR. The cytokine response was compared across the four groups using the Kruskal-Wallis test, followed by Dunn’s post hoc multiple comparisons. A): levels of TNF-alpha production by PBMCs with or without stimulations, B): levels of TNF-alpha in plasma, C):levels of IL-6 production by PBMCs with or without stimulations, D): levels of IL-6 in plasma; Unstim: unstimulated; PPD: purified protein derivative; SEB: staphylococcus enterotoxin B; HIV+LTB-: HIV positive-LTB negative; HIV+LTB+: HIV-LTB co-infected; HIV-LTB+: HIV negative- LTB positive; HIV-LTB-: HIV-negative and LTB-negative. *: p < 0.05, **: p < 0.01, ***: p < 0.001.
Fig 4.
The level of IL-17A in HIV-LTB co-infected and LTB-infected individuals was not significantly different.
PBMCs isolated from HIV+LTB- (n = 27), HIV+LTB+ (n = 13), HIV-LTB+ (n = 15) and HIV-LTB- (n = 15) were stimulated with media alone (Unstim), PPD or SEB and cultured for 19 hours at 37°C, and PBMC supernatants were harvested. The level of IL-17A was determined in plasma and from PBMC supernatants using a cytometric bead array. Data were presented in the median with IQR. The cytokine response was compared across the four groups using the Kruskal-Wallis test, followed by Dunn’s post hoc multiple comparisons. A): the level of IL-17A production by PBMCs with or without stimulation, B): level of IL-17A in plasma Unstim: unstimulated; PPD: purified protein derivative; SEB: staphylococcus enterotoxin B; HIV+LTB-: HIV positive-LTB negative; HIV+LTB+: HIV-LTB co-infected; HIV-LTB+: HIV negative- LTB positive; HIV-LTB-: HIV-negative and LTB-negative. *: p < 0.05, **: p < 0.01, ***: p < 0.001.
Fig 5.
HIV infection was associated with lower levels of mitogen-induced IL-10 in LTB-infected and LTB-negative individuals.
PBMCs isolated from HIV+LTB- (n = 27), HIV+LTB+ (n = 13), HIV-LTB+ (n = 15) and HIV-LTB- (n = 15) were stimulated with media alone (Unstim), PPD or SEB and cultured for 19 hours at 37°C, and PBMC supernatants were harvested. The levels of IL-4 and IL-10 were determined in plasma and from PBMC supernatants using a cytometric bead array. Data were presented using the median with IQR. The cytokine response was compared across the four groups using the Kruskal Wallis test, followed by Dunn’s post hoc multiple comparisons test to compare the median expression level of cytokines in each group. A): the level of IL4 expression by PBMCs with or without stimulation, B): the plasma level of L-4, C): the level of IL-10 production by PBMCs with or without stimulation, D): the plasma level of IL-10. Unstim: unstimulated; PPD: purified protein derivative; SEB: staphylococcus enterotoxin B; HIV+LTB-: HIV positive-LTB negative; HIV+LTB+: HIV-LTB co-infected; HIV-LTB+: HIV negative-LTB positive; HIV-LTB-: HIV-negative and LTB-negative. *: p < 0.05, **: p < 0.01, and ***: p < 0.001.