Expression of inhibitory regulators of innate immunity in patients with active tuberculosis

Abstract

BackgroundTuberculosis (TB) is an important cause of morbidity and mortality worldwide. Toll-like-receptors (TLRs) are important for the recognition of the causative agent Mycobacterium tuberculosis. Negative regulation of TLRs is necessary to control deleterious inflammatory damage, but could provide a means of immune evasion by M. tuberculosis as well.MethodsTo obtain insight in the extent of expression of inhibitory regulators of immunity in patients with active TB, peripheral-blood-mononuclear-cells (PBMCs) and plasma were obtained from 54 TB patients and 29 healthy blood donors from Chittagong, Bangladesh. Bilateral alveolar macrophages were obtained from an infected versus a contralateral normal lung segment of 9 patients. Statistical analyses were performed using Mann–Whitney U and Wilcoxon matched pairs testing. Correlations were calculated using the Spearman rho test.ResultsPBMCs harvested from TB patients demonstrated increased mRNA expression of IL-1-receptor-associated-kinase-M, suppressor-of-cytokine-signalling-3 and Toll-interacting-protein. Flow cytometry revealed enhanced expression of IL-1-receptor-like-1 (ST2) on lymphocytes. Plasma soluble ST2 was elevated in patients with TB and correlated with established TB biomarkers, most strongly with soluble interleukin-2 receptor subunit α and interleukin-8. Alveolar macrophage mRNA expression of negative TLR regulators did not differ between the infected and contralateral lung side.ConclusionThese results show enhanced expression of distinct negative regulators of innate immunity in PBMCs of patients with TB and identify plasma soluble ST2 as a potential novel biomarker for TB disease activity.

Tumor-associated macrophages in cancers

“…Pulmonary TAMs are important component of the pulmonary innate immunity, participating in phagocytosis and removal of the alien dust particles or pathogens and antigen presentation [52]. Macrophages in nests and tumor stromal have different biological characteristics and functions.…”

HCV core protein binds to gC1qR to induce A20 expression and inhibit cytokine production through MAPKs and NF-κB signaling pathways

“…In addition, activated macrophages can also produce multiple negative regulators [28, 29]. The negative regulators contribute to inhibit further activation of inflammatory signaling pathways, thereby, protect the host from excessive immune responses [30, 31]. …”

Neutrophil extracellular traps in patients with pulmonary tuberculosis

“…Additionally, elastase can activate macrophages and increase their capacity to kill intracellular pathogens [ 14 ]. Moreover, macrophages can bind M. tuberculosis induced NETs and ingest elastase from neutrophils, leading to the release of increased amounts of proinflammatory cytokines [ 7 ] like we found in the tuberculosis patients included in this study [ 11 ]. Together these data suggest that during tuberculosis elastase could be involved in an interaction between NETotic cells and macrophages resulting in a proinflammatory and protective immune response.…”

“…Written informed consent was obtained from all study subjects or next-of-kin by a native Bengali speaker. These subjects were part of a larger population in which the expression of Toll-like receptor regulators was studied [ 11 ]. Inclusion and exclusion criteria have been reported in detail [ 11 ].…”

“…These subjects were part of a larger population in which the expression of Toll-like receptor regulators was studied [ 11 ]. Inclusion and exclusion criteria have been reported in detail [ 11 ]. The study subjects were all newly registered patients who had not (yet) received therapy at the time of enrolment.…”