MTB driven B cells producing IL-35 and secreting high level of IL-10 in the patients with active pulmonary tuberculosis

Elevation in the counts of IL-35-producing B cells infiltrating into lung tissue in mycobacterial infection is associated with the downregulation of Th1/Th17 and upregulation of Foxp3+Treg

“…IL-35 negatively regulated the development of autoimmune disease by inducing the generation and expansion of IL-10-producing B cells 26 . A previous study indicated that IL-35-producing B cells in patients with active TB possessed a stronger ability to produce more IL-10 33 . This study also aimed to determine whether the mycobacterial infection in mice could induce IL-10 production in IL-35-producing B cells.…”

“…A previous study showed that IL-35 was upregulated in serum in patients with active TB and was related to the activation of Treg cells 32 . IL-35 was produced by B cells, with a strong ability to produce IL-10, in the peripheral blood in patients with active TB and in human tuberculous granuloma 33 . For further understanding the roles of IL-35 played in pulmonary tuberculosis, a mouse model was prepared with M. bovis BCG infection (Fig.…”

“…More recently, it was reported that IL-35-producing B cells infiltrated into the tuberculous granuloma of patients with ATB, and the mRNA expression of both subunits of IL-35 ( p35 and Ebi3 ) in purified B cells from patients with ATB was elevated. Furthermore, purified B cells from patients with ATB produced more IL-35 after stimulation by Mtb antigen, and the IL-35-producing B cells expressed the high level of IL-10 33 . However, the function and underlying mechanisms of IL-35-producing B cells in TB progression have not been investigated.…”

Target the Host, Kill the Bug; Targeting Host Respiratory Immunosuppressive Responses as a Novel Strategy to Improve Bacterial Clearance During Lung Infection

“…Bregs were also shown to have inhibitory effects on IL-22 production (86), a cytokine implicated in limiting M. tuberculosis intracellular survival (87,88). More recent studies have demonstrated how circulating Bregs of active M. tuberculosisinfected patients were producing the immunoregulatory cytokine IL-35 (89), a potent immunosuppressive cytokine capable of suppressing effector T cell responses, promoting the expansion of Tregs and their production of IL-10 (90). Additionally, stimulating purified B cells from healthy controls with M. tuberculosis lysate, increased expansion of IL-35 + Bregs (89), suggesting M. tuberculosis may be inducing the production of IL-35 by Bregs to enhance IL-10 production to regulate inflammatory responses.…”

“…Bruton's tyrosine kinase (BTK) inhibitors which are approved for treatment of B cell lymphomas have the capacity to block both BCR signaling and STAT3 activation and are capable of reducing IL-10 production and PD-L1 expression in B cells (161). The use of these inhibitors to specifically target Breg cells could potentially be used to treat infections such as M. tuberculosis which has been shown to subvert Breg responses (85,89).…”