CHARACTERIZATION OF INTERFERON-γ PRODUCING CELLS IN THE PERIPHERAL BLOOD OF PATIENTS WITH TUBERCULOSIS

Abstract

Abstract Tuberculosis (TB) caused 1.4 million deaths in 2015. The infection starts when Mycobacterium tuberculosis is inhaled and interacts with immune cells in the respiratory tract. Alveolar macrophages, neutrophils and dendritic cells (DCs) engulf the mycobacteria; these DCs migrate to the draining lymph node and induce the activation of mycobacteria-specific Th cells. These Th cells migrate back to the lung and produce IFNγ and TNFα, two cytokines essential for mycobacterial control. In addition to Th cells, other cells, such as Tγδ and NK cells, produce IFNγ in response to mycobacteria; innate lymphoid cells (ILCs) are also able to produce IFNγ, but it still unknown if ILCs, which have been detected in human lungs during cancer, produce this cytokine in response to mycobacteria. We evaluated, by flow cytometry, the frequency and IFNγ production of Th, Tγδ, NK and ILCs (ILC1, ILC2 and ILC3) in the peripheral blood of healthy individuals (negative and positive for the Quantiferon [QTF] test, which detects latent TB), and patients with active pulmonary TB. The numbers of Th, Tγδ, NK cells and ILCs (ILC1, ILC2 and ILC3) were decreased in TB patients. Peripheral blood was stimulated with M. tuberculosis soluble extract for 5 h in the presence of brefeldin A. In healthy, QTF-negative individuals, IFNγ production was increased in Tγδ and ILC2 after stimulation; in healthy, QTF-positive individuals, IFNγ production was increased in Th, Tγδ and ILCs, and in TB patients, IFNγ production was increased in NK cells and ILC2. These results suggest ILCs produce IFNγ during TB infection. This project was funded by SIP-IPN-México (20170616).