Immunomodulatory activity of 4-(Benzyloxy)phenol facilitates intracellular mycobacterial clearance through p53 mediated IL-35 signaling dependent JAK1/STAT3 pathway in human macrophages

Goletti D, Meintjes G, Andrade BB, Zumla A, Shan Lee S. Insights from the 2024 WHO global tuberculosis report - more comprehensive action, innovation, and investments required for achieving WHO End TB goals. Int J Infect Dis. 2025;150:107325.

Article  PubMed  Google Scholar 

Singh A, Prasad R, Balasubramanian V, Gupta N. Drug-resistant tuberculosis and HIV infection: current perspectives. HIV/AIDS (Auckland, NZ). 2020;12:9.

CAS  Google Scholar 

Katelaris AL, Jackson C, Southern J, Gupta RK, Drobniewski F, Lalvani A, Lipman M, Mangtani P, Abubakar I. Effectiveness of BCG vaccination against Mycobacterium tuberculosis infection in adults: a cross-sectional analysis of a UK-based cohort. J Infect Dis. 2020;221(1):146–55.

Article  CAS  PubMed  Google Scholar 

Li D, Wu M. Pattern recognition receptors in health and diseases. Signal Transduct Target Ther. 2021;6(1):291.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sampath P, Rajamanickam A, Thiruvengadam K, Natarajan AP, Hissar S, Dhanapal M, Thangavelu B, Jayabal L, Ramesh PM, Ranganathan UD. Cytokine upsurge among drug-resistant tuberculosis endorse the signatures of hyper inflammation and disease severity. Sci Rep. 2023;13(1):785.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cooper AM, Khader SA. The role of cytokines in the initiation, expansion, and control of cellular immunity to tuberculosis. Immunol Rev. 2008;226(1):191–204.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Harris J, Keane J. How tumour necrosis factor blockers interfere with tuberculosis immunity. Clin Exp Immunol. 2010;161(1):1–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang SY, Boisson-Dupuis S, Chapgier A, Yang K, Bustamante J, Puel A, Picard C, Abel L, Jouanguy E, Casanova JL. Inborn errors of interferon (IFN)-mediated immunity in humans: insights into the respective roles of IFN-α/β, IFN-γ, and IFN-λ in host defense. Immunol Rev. 2008;226(1):29–40.

Article  CAS  PubMed  Google Scholar 

Tiwari D, Martineau AR. Inflammation-mediated tissue damage in pulmonary tuberculosis and host-directed therapeutic strategies. Seminars in Immunology. 2023;65:101672.

Article  CAS  PubMed  Google Scholar 

Orme IM, Robinson RT, Cooper AM. The balance between protective and pathogenic immune responses in the TB-infected lung. Nat Immunol. 2015;16(1):57–63.

Article  CAS  PubMed  Google Scholar 

Nienaber A, Hayford FE, Variava E, Martinson N, Malan L. The manipulation of the lipid mediator metabolism as adjunct host-directed therapy in tuberculosis. Front Immunol. 2021;12:623941.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xie Q, Xu W-D, Pan M, Lan Y-Y, Liu X-Y, Su L-C, Huang A-F. Association of IL-35 expression and gene polymorphisms in rheumatoid arthritis. Int Immunopharmacol. 2021;90:107231.

Article  CAS  PubMed  Google Scholar 

Gao L, Xiong Y-J, Liang Y-X, Huang P-F, Liu S, Xiao Y, Huang Q, Wang H, Wu H-M. The effects of IL-27 and IL-35 gene variation and expression levels on the susceptibility and clinical manifestations of pulmonary tuberculosis. Front Immunol. 2024;15:1267624.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM, Cross R, Sehy D, Blumberg RS, Vignali DAA. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature. 2007;450(7169):566–9.

Article  CAS  PubMed  Google Scholar 

Zhang J, Zhang Y, Wang Q, Li C, Deng H, Si C, Xiong H. Interleukin-35 in immune-related diseases: protection or destruction. Immunology. 2019;157(1):13–20.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ye C, Yano H, Workman CJ, Vignali DAA. Interleukin-35: Structure, Function and Its Impact on Immune-Related Diseases. J Interferon Cytokine Res. 2021;41(11):391–406.

Article  PubMed  PubMed Central  Google Scholar 

Wang L, Qi Y, Nan Y, Qi S. Role of IFN-γ, IL-33, and IL-35 concentrations in tuberculous pleural effusion in diagnosis and analysis of the effectiveness of combined tests. Medicine. 2024;103(47):e40375.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dai Y-C, Wang W-D, Zhang J-A, Chen C, Luo H-L, Xu H, Peng Y, Luo H, Yang X-R, Chen X. MTB driven B cells producing IL-35 and secreting high level of IL-10 in the patients with active pulmonary tuberculosis. Mol Immunol. 2019;112:175–81.

Article  CAS  PubMed  Google Scholar 

A. Mishra, A. Behura, A. Kumar, A. Ghosh, L. Naik, S. Mawatwal, S.S. Mohanty, A. Mishra, S. Saha, S.K. Bhutia, Soybean lectin induces autophagy through P2RX7 dependent activation of NF-κB-ROS pathway to kill intracellular mycobacteria. Biochimica et Biophysica Acta (BBA)-General Subjects 1865(2) (2021) 129806

Mawatwal S, Behura A, Mishra A, Singh R, Dhiman R. Calcimycin induced IL-12 production inhibits intracellular mycobacterial growth by enhancing autophagy. Cytokine. 2018;111:1–12.

Article  CAS  PubMed  Google Scholar 

A. Mishra, A. Kumar, L. Naik, S. Patel, M. Das, A. Behura, D.K. Nayak, A. Mishra, S.K. Bhutia, R.J.C. Singh, Soybean lectin-triggered IL-6 secretion induces autophagy to kill intracellular mycobacteria through P2RX7 dependent activation of the JAK2/STAT3/Mcl-1 pathway, 171 (2023) 156366.

Kumar A, Naik L, Patel S, Das M, Nayak DK, Mishra A, Mishra A, Singh R, Behura A, Dhiman R. Ac-93253 inhibits intracellular growth of mycobacteria in human macrophages by inducing apoptosis in mitochondrial-dependent manner. Biochimica et Biophysica Acta (BBA) - General Subjects. 2023;1867(9):130425.

S. Mawatwal, A. Behura, A. Ghosh, S. Kidwai, A. Mishra, A. Deep, S. Agarwal, S. Saha, R. Singh, R. Dhiman, Calcimycin mediates mycobacterial killing by inducing intracellular calcium-regulated autophagy in a P2RX7 dependent manner. Biochimica Et Biophysica Acta (BBA)-General Subjects 1861(12) (2017) 3190–3200

Patel S, Naik L, Das M, Nayak DK, Dandsena PK, Mishra A, Kumar A, Dirisala VR, Mishra A, Das S. Furamidine-induced autophagy exerts an anti-mycobacterial effect in a SIRT1-pAMPK-FOXO3a-dependent manner by elevation of intracellular Ca2+ level expression. Microbiol Res. 2025;290:127976.

Article  CAS  PubMed  Google Scholar 

Naik L, Patel S, Kumar A, Ghosh A, Mishra A, Das M, Nayak DK, Saha S, Mishra A, Singh R, Behura A, Dhiman R. 4-(Benzyloxy)phenol-induced p53 exhibits antimycobacterial response triggering phagosome-lysosome fusion through ROS-dependent intracellular Ca2+ pathway in THP-1 cells. Microbiol Res. 2024;282:127664.

Article  CAS  PubMed  Google Scholar 

Chaturvedi V, Collison LW, Guy CS, Workman CJ, Vignali DA. Cutting edge: human regulatory T cells require IL-35 to mediate suppression and infectious tolerance. J Immunol. 2011;186(12):6661–6.

Article  CAS  PubMed  Google Scholar 

Collison LW, Delgoffe GM, Guy CS, Vignali KM, Chaturvedi V, Fairweather D, Satoskar AR, Garcia KC, Hunter CA, Drake CG. The composition and signaling of the IL-35 receptor are unconventional. Nat Immunol. 2012;13(3):290–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kong B, Liu G-B, Zhang J-A, Fu X-X, Xiang W-Y, Gao Y-C, Lu Y-B, Wu X-J, Qiu F, Wang W-D. Elevated serum IL-35 and increased expression of IL-35-p35 or-EBI3 in CD4+ CD25+ T cells in patients with active tuberculosis. Am J Translational Res. 2016;8(2):623.

CAS  Google Scholar 

Yu F, Zhu X, Li Q, Xu W, Gao Y, Wen Y, Zhang Q, Dou J. Elevated IL-35 level and iTr35 subset increase the bacterial burden and lung lesions in Mycobacterium tuberculosis-infected mice. Open Life Sci. 2022;17(1):312–20.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dong Y, Li X, Yu Y, Lv F, Chen Y. JAK/STAT signaling is involved in IL-35-induced inhibition of hepatitis B virus antigen-specific cytotoxic T cell exhaustion in chronic hepatitis B. Life Sci. 2020;252:117663.

Article  CAS  PubMed  Google Scholar 

Zhu Z, Zhang Y, Ye J, Wang X, Fu X, Yin Y, Wen J, Wu X, Xia Z. IL-35 promoted STAT3 phosphorylation and IL-10 production in B cells, but its production was reduced in patients with coronary artery diseases. Hum Immunol. 2018;79(12):869–75.

Article  CAS  PubMed  Google Scholar 

Ma Y, Chen L, Xie G, Zhou Y, Yue C, Yuan X, Zheng Y, Wang W, Deng L, Shen L. Elevated level of interleukin-35 in colorectal cancer induces conversion of T cells into iTr35 by activating STAT1/STAT3. Oncotarget. 2016;7(45):73003.

Article  PubMed  PubMed Central 

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