Mycobacterium tuberculosis-specific cytokine responses of infants born to mothers with active tuberculosis in Uganda

BackgroundImmunizing infants with various vaccines, including Bacillus Calmette-Guerin (BCG), Diphtheria-Pertusis-Tetanus (DPT), and measles, aims to enhance immunity. In instances where vaccine responses have been reported to be compromised, individuals are prone to infection. The BCG vaccine, for example, induces strong type 1 immune responses, particularly interferon-gamma (IFN-{gamma}) expression, that are essential for protection against Mycobacterium tuberculosis (Mtb). However, there is scanty evidence on whether this effect is established or sustained when infants are exposed to Mtb either in utero or after birth. We compared TB-specific cytokine responses for IFN-{gamma}, interleukin (IL)-2 (IL-2), tumour necrosis factor-alpha (TNF-), IL-17A, and Granulocyte-macrophage colony-stimulating factor (GM-CSF) using supernatants harvested from QFT-Plus Blood Collection Tubes. MethodsThis cross-sectional study compared 22 infants born to mothers with bacteriologically confirmed active tuberculosis (TB), defined as TB exposed or cases, to 20 infants born to mothers without active TB, defined as TB non-exposed or controls. Plasma harvested from the QFT-plus tubes (TB1 and TB2) was used to perform a 5-plex Luminex assay using the LX 100/200 Luminex machine and measured in pg/mL. Data was analysed using R (v.4.4.1). The Mann-Whitney U test was used to determine statistical significance at a p-value less than 0.05 and a 95% confidence interval. Data was expressed as median and interquartile ranges (IQR). ResultsTB-exposed infants showed IFN{gamma} responses were slightly higher among TB-exposed infants compared to non-exposed (Medians (IQR): 15.49 (14.58-16.49) versus 14.96 (14.60-16.60), p=0.68, respectively. There was a strong expression of total IL-17A among TB-exposed compared to non-exposed 11.91 (10.89-13.50) versus 10.69 (10.17-11.64), p=0.035. We observed no differences in IL-2, TNF, and GM-CSF responses. ConclusionTB exposure among infants slightly alters their Mtb-specific cytokine responses, especially IL-17A cytokine responses. This suggests possible ongoing Mtb infection among TB-exposed infants. Follow-up studies of such infants are necessary to assess their risk of future TB infection and disease and the potential need for TB chemoprophylaxis.