Innate lymphoid cells exhibited IL-17-expressing phenotype in active tuberculosis disease

Abstract

Background Innate lymphoid cells (ILCs), as an important group of innate immunity, could respond rapidly to Mycobacterium tuberculosis (Mtb) infection. In this research, we studied the phenotypic changes of circulatory ILCs in active tuberculosis (TB) disease. Methods We recruited 40 patients with active Mtb infection (TB group) and 41 healthy subjects (NC group), and collected their clinical information and peripheral blood. Circulating ILCs, ILC subsets, dendritic cells (DCs), macrophages, and the production of cytokines in ILCs were tested by flow cytometry (FCM). Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma IL-23. Results Compared with healthy control, total ILCs (0.73% vs. 0.42%, P = 0.0019), ILC1 (0.55% vs. 0.31%, P = 0.0024) and CD117+ ILC2 (0.02% vs. 0.01%, P = 0.0267) were upregulated in TB group. The total IL-17+ lymphocytes were elevated (3.83% vs. 1.76%, P = 0.0006) while the IL-22+ lymphocytes remained unchanged. Within ILC subsets, ILC3, CD117+ ILC2 and ILC1 in TB group all expressed increased IL-17 (15.15% vs. 4.55%, 19.01% vs. 4.57%, 8.79% vs. 3.87%, P < 0.0001) but similar IL-22 comparing with healthy control. TB group had more plasma IL-23 than NC group (7.551 vs. 5.564 pg/mL, P = 0.0557). Plasma IL-23 in TB group was positively correlated to IL-17+ ILC3 (r = 0.4435, P = 0.0141), IL-17+CD117+ ILC2 (r = 0.5385, P = 0.0021) and IL-17+ ILC1(r = 0.3719, P = 0.0430). TB group also had elevated DCs (9.35% vs. 6.49%, P < 0.0001) while macrophages remained unchanged. Within TB group, higher proportion of IL-17+ ILCs was related to severer inflammatory status and poorer clinical condition. Conclusions In active TB disease, circulatory ILCs were upregulated and exhibited IL-17-expressing phenotype. This may expand the understanding of immune reaction to Mtb infection.

Innate Lymphoid Cells in Response to Intracellular Pathogens: Protection Versus Immunopathology

“…Moreover, protection against Mtb after BCG vaccination correlated with expansion of T-bet + ILC1s and IFNγ production, indicating the protective role of ILC1s in mouse model ( Steigler et al., 2018 ; Corral et al., 2021 ). Consistent with this data, recent study showed increased numbers of IFNγ-producing ILC1s in the blood of active tuberculosis patients ( Pan et al., 2021 ).…”

Differential activation of innate and adaptive lymphocytes during latent or active infection with Mycobacterium tuberculosis

“…In this model, ILC1s and ILC2s produce TNF-α, while ILC3s produce GM-CSF and IL-22, but not IL-17. 8 However, Pan et al 63 reported that the three peripheral blood ILC subsets from active TB patients produce IL-17 after activation with PMA and ionomycin, and that this IL-17 production correlates with the presence clinical symptoms. MTSE contains PAMPs that can directly activate NK cells and ILCs.…”

Immunologic Role of Innate Lymphoid Cells against Mycobacterial tuberculosis Infection

“…The inflammatory environment caused by M. tb infection leads to the differentiation of IL-18Rα+ ILCs into ILC1-like cells (characterized by the expression of T-bet), the functions of which resulted in decreased bacterial loads upon M. tb challenge [ 33 ]. In assays conducted by Pan et al, an analysis of blood samples collected from patients with active M. tb infection revealed a marked expansion of group 1 ILCs compared with samples from healthy patients [ 36 ]. This expansion of ILC1 population in blood samples with active tuberculosis also revealed increased production of IL-17, a proinflammatory cytokine, from ILC1s.…”

“…This expansion of ILC1 population in blood samples with active tuberculosis also revealed increased production of IL-17, a proinflammatory cytokine, from ILC1s. Pan et al also found that in patients with active M. tb infection, upregulation of DCs resulted in increased IL-23 secretion, driving greater differentiation of IL-17+ ILC1s relative to IFN-γ+ ILC1s [ 36 ]. As a result, in addition to IL-17 secretion from γδ T cells, secretion of IL-17 by group 1 ILCs further promotes granulopoiesis, neutrophil migration, and stimulates the innate immune response [ 36 , 37 ].…”

“…By way of flow cytometry, Pan et al calculated differences in ILC response in healthy human subjects compared with individuals infected by M. tb . The results revealed that individuals infected with M. tb had significantly increased levels of all ILC subtypes, including ILC3, and more importantly, increased IL-17 secretion without significant changes pertaining to IL-22 secretion [ 36 ]. As a result, the relationship between RORγt and ILC3 function indicates that RORγt expression enhances immune defense against M. tb infection [ 59 ].…”