Abstract
The complement system is activated in tuberculous pleural effusion (TPE), with increased levels of the anaphylatoxins stimulating pleural mesothelial cells (PMCs) to secrete chemokines, which recruit nonclassical monocytes to the pleural cavity. The differentiation and recruitment of naive CD4+ T cells are induced by pleural cytokines and PMC-produced chemokines in TPE. However, it is unclear whether anaphylatoxins orchestrate CD4+ T cell response via interactions between PMCs and monocytes in TPE. In this study, CD16+ and CD16- monocytes isolated from TPE patients were cocultured with PMCs pretreated with anaphylatoxins. After removing the PMCs, the conditioned monocytes were cocultured with CD4+ T cells. The levels of the cytokines were measured in PMCs and monocyte subsets treated separately with anaphylatoxins. The costimulatory molecules were assessed in conditioned monocyte subsets. Furthermore, CD4+ T cell response was evaluated in different coculture systems. The results indicated that anaphylatoxins induced PMCs and CD16+ monocytes to secrete abundant cytokines capable of only inducing Th17 expansion, but Th1 was feeble. In addition, costimulatory molecules were more highly expressed in CD16+ than in CD16− monocytes isolated from TPE. The interactions between monocytes and PMCs enhanced the ability of PMCs and monocytes to produce cytokines and that of monocytes to express HLA-DR, CD40, CD80 and CD86, which synergistically induced Th17 expansion. In the above process, anaphylatoxins enhanced the interactions between monocytes and PMCs by increasing the level of the cytokines IL-1β, IL-6, IL-23 and upregulating the phenotype of CD40 and CD80 in CD16+ monocytes. Collectively, these data indicate that anaphylatoxins play a central role in orchestrating Th17 response mainly via interactions between CD16+ monocytes and PMCs in TPE.
Highlights
Tuberculous pleural effusion (TPE), one of the common forms of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis (Mtb) infection [1], is characterized by intense chronic accumulations of fluid and lymphocyte cells[2,3,4] and monocytes/macrophages [5], in the pleural space.Complement mediators play important roles in providing protection against Mtb [6, 7]
Costimulatory molecules were more highly expressed in CD16+ than in CD16− monocytes isolated from TPE
The interactions between monocytes and pleural mesothelial cells (PMCs) enhanced the ability of PMCs and monocytes to produce cytokines and that of monocytes to express HLA-DR, CD40, CD80 and CD86, which synergistically induced Th17 expansion
Summary
Tuberculous pleural effusion (TPE), one of the common forms of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis (Mtb) infection [1], is characterized by intense chronic accumulations of fluid and lymphocyte cells[2,3,4] and monocytes/macrophages [5], in the pleural space.Complement mediators play important roles in providing protection against Mtb [6, 7]. Tuberculous pleural effusion (TPE), one of the common forms of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis (Mtb) infection [1], is characterized by intense chronic accumulations of fluid and lymphocyte cells[2,3,4] and monocytes/macrophages [5], in the pleural space. Our previous study demonstrated that the complement system was activated in TPE [5]. There are three activation pathways resulting in the generation of multiple effector molecules, including the anaphylatoxins C3a and C5a [8, 9], which induce monocyte [10], T lymphocyte [11] and neutrophil [12] chemoattraction and activation through binding to the receptors C3aR and C5aR, respectively. Our previous research found that C3a and C5a stimulated pleural mesothelial cells (PMCs) isolated from the pleural cavity to secrete the chemokines CCL2, CCL7, and CX3CL1, which recruited nonclassical monocytes (NCMs) [5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
