IL-17 and IL-22 Positive Innate Lymphoid Cells Mediate Early Immunization of Lung Mass Type Tuberculosis

Abstract

Aim: Activated innate immunity is a crucial early response to protect against the proliferation and spread of Mycobacterium tuberculosis (Mtb). Innate immune cells, such as neutrophils, dendritic cells and macrophages, have been found to play important roles in inactivating Mtb. However, there are currently few studies on the role of innate lymphoid cells(ILCs) in Mtb infection, as well as its different subtypes compared with lung cancer is scarcely studied. In particular, the role of ILCs in distinguishing the difference in the lung mass between tuberculosis and lung cancer has not been reported yet. Methods:We collected blood samples from healthy subjects, patients with lung mass diagnosed as untreated tuberculosis and patients with lung mass diagnosed as lung cancer. Differences of innate immune cells (dendritic cells, macrophages, neutrophils, ILCs and its subsets) and adaptive immune cells (T cells and B cells) in the above three groups were analyzed by flow cytometry.Results:Compared with healthy subjects, patients with Mtb infection presented increased level of macrophages and neutrophils but decreased B cells and T cells in circulating blood, while dendritic cell is remained unchanged. The ILCs were upregulated in Mtb infection patients compared with healthy subjects, among which the subtypes group 2 ILC (ILC2), particularly the CD117+ILC2 were increased while group 1 and 3 ILCs (ILC1, ILC3) were intact. However,the proportion of IL-17 and IL-22-secreting cells were also increased both in ILC1 and CD117+ILC2. In addition, there were no differences in neutrophils and T cells between Mtb infection group and lung cancer group, but Mtb-infected patients showed higher dendritic cells and B cells. As for ILCs, surprisingly, Mtb patients showed more CD117-ILC2 than lung cancer patients, but the proportion of IL-17 and IL-22-producing cells were both upregulated in the subsets of ILC2, regardless of CD117 expression. Besides, the IL-17 and IL-22-secreting cells were also increased in ILC1s while the total number of ILC1 was unchanged.Conclusions: By comparing changes of immune cells in the circulation, we found that CD117+ ILC2 which has ILC3-like characters were up-regulated in response to Mtb infection, and the ability to producing IL-17 and IL-22 was enhanced. When compared with lung cancer, Mtb infection presented higher CD117-ILC2 (classical ILC2) which had promoted capability of secreting IL-17 and IL-22. Consequently, it is implied that when infected by Mtb, ILC2 is activated into a pro-inflammatory subset with enhanced IL-17 and IL-22 secretion which may have tendency to transit to ILC3.