Furamidine enhances IL-23-mediated autophagic response through IL-23R-TYK2-STAT3-dependent regulation of intracellular Ca²⁺ level to facilitate mycobacterial clearance in human macrophages

Zhai W et al (2019) The immune escape mechanisms of Mycobacterium tuberculosis. Int J Mol Sci 20(2):340

Article  PubMed  PubMed Central  Google Scholar 

Cohen SB et al (2018) Alveolar macrophages provide an early Mycobacterium tuberculosis niche and initiate dissemination. Cell Host Microbe 24(3):439–446e4

Article  PubMed  PubMed Central  CAS  Google Scholar 

Cooper AM, Mayer-Barber KD, Sher A (2011) Role of innate cytokines in mycobacterial infection. Mucosal Immunol 4(3):252–260

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ahmad S (2011) Pathogenesis, immunology, and diagnosis of latent Mycobacterium tuberculosis infection. J Immunol Res 2011(1):814943

Google Scholar 

Goletti D et al (2025) 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, 150

Domingo-Gonzalez R et al (2016) Cytokines and chemokines in Mycobacterium tuberculosis infection. Microbiol Spectr 4(5).

Yamashita Y et al (2019) CD4 + T responses other than Th1 type are preferentially induced by latency-associated antigens in the state of latent Mycobacterium tuberculosis infection. Front Immunol 10:2807

Article  PubMed  PubMed Central  CAS  Google Scholar 

Giacomini E et al (2001) Infection of human macrophages and dendritic cells with Mycobacterium tuberculosis induces a differential cytokine gene expression that modulates T cell response. J Immunol 166(12):7033–7041

Article  PubMed  CAS  Google Scholar 

Lam A et al (2017) Role of apoptosis and autophagy in tuberculosis. Am J Physiology-Lung Cell Mol Physiol 313(2):L218–L229

Article  Google Scholar 

Mishra A et al (2023) Soybean lectin-triggered IL-6 secretion induces autophagy to kill intracellular mycobacteria through P2RX7 dependent activation of the JAK2/STAT3/Mcl-1 pathway. Cytokine 171:156366

Article  PubMed  CAS  Google Scholar 

Mawatwal S et al (2018) Calcimycin induced IL-12 production inhibits intracellular mycobacterial growth by enhancing autophagy. Cytokine 111:1–12

Article  PubMed  CAS  Google Scholar 

Floss DM, Moll JM, Scheller J (2020) IL-12 and IL-23—close relatives with structural homologies but distinct immunological functions. Cells 9(10):2184

Article  PubMed  PubMed Central  CAS  Google Scholar 

Khader SA, Cooper AM (2008) IL-23 and IL-17 in tuberculosis. Cytokine 41(2):79–83

Article  PubMed  PubMed Central  CAS  Google Scholar 

Kelsey A, Chirch LM, Payette MJ (2018) Tuberculosis and Interleukin blocking monoclonal antibodies: is there risk? Dermatol Online J, 24(9)

Wang H et al (2025) The role and potential application of IL-12 in the immune regulation of tuberculosis. Int J Mol Sci 26(7):3106

Article  PubMed  PubMed Central  CAS  Google Scholar 

Di Cesare A, Meglio PD, Nestle FO (2009) The IL-23/Th17 axis in the Immunopathogenesis of psoriasis. J Invest Dermatology 129(6):1339–1350

Article  Google Scholar 

Parham C et al (2002) A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rβ1 and a novel cytokine receptor subunit, IL-23R. J Immunol 168(11):5699–5708

Article  PubMed  CAS  Google Scholar 

Camard L et al (2025) IL-23 tunes inflammatory functions of human mucosal-associated invariant T cells. iScience, 28(2)

Philippot Q et al (2023) Human IL-23 is essential for IFN-γ–dependent immunity to mycobacteria. Sci Immunol 8(80):eabq5204

Article  PubMed  PubMed Central  CAS  Google Scholar 

Shen H et al (2015) Th17-related cytokines contribute to recall‐like expansion/effector function of HMBPP‐specific Vγ2Vδ2 T cells after Mycobacterium tuberculosis infection or vaccination. Eur J Immunol 45(2):442–451

Article  PubMed  PubMed Central  CAS  Google Scholar 

Rai PK et al (2016) A novel therapeutic strategy of lipidated promiscuous peptide against Mycobacterium tuberculosis by eliciting Th1 and Th17 immunity of host. Sci Rep 6(1):23917

Article  PubMed  PubMed Central  CAS  Google Scholar 

Shen H, Chen ZW (2018) The crucial roles of Th17-related cytokines/signal pathways in M. tuberculosis infection. Cell Mol Immunol 15(3):216–225

Article  PubMed  CAS  Google Scholar 

Khader SA et al (2007) IL-23 and IL-17 in the establishment of protective pulmonary CD4 + T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat Immunol 8(4):369–377

Article  PubMed  CAS  Google Scholar 

Ritter K et al (2021) Interleukin-23 instructs protective multifunctional CD4 T cell responses after immunization with the Mycobacterium tuberculosis subunit vaccine H1 DDA/TDB independently of interleukin-17A. J Mol Med 99:1585–1602

Article  PubMed  CAS  Google Scholar 

Campoy E, Colombo MI (2009) Autophagy in intracellular bacterial infection. (BBA)-Molecular Cell Res 1793(9):1465–1477Biochimica et Biophysica Acta

CAS  Google Scholar 

Sun R, Abraham C (2020) IL23 promotes antimicrobial pathways in human macrophages, which are reduced with the IBD-protective IL23R R381Q variant. Cell Mol Gastroenterol Hepatol 10(4):673–697

Article  PubMed  PubMed Central  Google Scholar 

Arnison PG et al (2013) Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat Prod Rep 30(1):108–160

Article  PubMed  PubMed Central  CAS  Google Scholar 

Hlaka L (2019) Investigation of minor groove binders (MGB), non-ionic surfactant vesicles (NIV) delivery systems and IL-4i1 as novel pathogen- and host-directed drug therapy for tuberculosis

Patel S et al (2025) Furamidine-induced autophagy exerts an anti-mycobacterial effect in a SIRT1-pAMPK-FOXO3a-dependent manner by elevation of intracellular Ca2 + level expression. Microbiol Res 290:127976

Article  PubMed  CAS  Google Scholar 

Naik L et al (2024) 4-(Benzyloxy) phenol-induced p53 exhibits antimycobacterial response triggering phagosome-lysosome fusion through ROS-dependent intracellular Ca2 + pathway in THP-1 cells. Microbiol Res, : p. 127664

Mawatwal S et al (2017) Calcimycin mediates mycobacterial killing by inducing intracellular calcium-regulated autophagy in a P2RX7 dependent manner. Biochimica et biophysica acta (BBA)-General subjects. 1861(12):3190–3200

Mishra A et al (2021) 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):129806

Behura A et al (2019) ESAT-6 modulates Calcimycin-induced autophagy through microRNA-30a in mycobacteria infected macrophages. J Infect 79(2):139–152

Article  PubMed  Google Scholar 

Kumar A et al (2023) Ac-93253 inhibits intracellular growth of mycobacteria in human macrophages by inducing apoptosis in mitochondrial-dependent manner. Biochimica et biophysica acta (BBA)-General subjects. 1867(9):130425

Behura A et al (2021) ESAT-6 impedes IL-18 mediated phagosome lysosome fusion via microRNA-30a upon calcimycin treatment in mycobacteria infected macrophages. Int Immunopharmacol 101:108319

Article  PubMed  CAS  Google Scholar 

Singh A et al (2024) Prolonged glutamine starvation reactivates mTOR to inhibit autophagy and initiate autophagic lysosome reformation to maintain cell viability. Int J Biochem Cell Biol 177:106694

Article  PubMed  CAS  Google Scholar 

Praharaj PP et al (2023) Co-targeting autophagy and NRF2 signaling triggers mitochondrial superoxide to sensitize oral cancer stem cells for cisplatin-induced apoptosis. Free Radic Biol Med 207:72–88

Article  PubMed  CAS  Google Scholar 

Zhou X et al (2019) Different signaling pathways define different interferon-stimulated gene expression during mycobacteria infection in macrophages. Int J Mol Sci 20(3):663

Article  PubMed  PubMed Central  CAS  Google Scholar 

Chandra P, Grigsby SJ, Philips JA (2022) Immune evasion and provocation by Mycobacterium tuberculosis. Nat Rev Microbiol 20(12):750–766

Article  PubMed  PubMed Central  CAS 

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