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Review

The use of immunotherapy for the treatment of tuberculosis

, , , &
Pages 427-440 | Received 08 Jan 2018, Accepted 22 Mar 2018, Published online: 27 Mar 2018

References

  • WHO. Global tuberculosis report 2017. Geneva: World Health Organization; 2017.
  • Kumar A, Kumar AMV, Gupta D, et al. Global guidelines for treatment of tuberculosis among persons living with HIV: unresolved issues. Int J Tuberc Lung Dis. 2012;16:573–578.
  • Raviglione M, Sulis G. Tuberculosis 2015: burden, challenges and strategy for control and elimination. Infect Dis Rep. 2016;8:33–37.
  • Ramappa V, Aithal GP. Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management. J Clin Exp Hepatol. 2013;3:37–49.
  • Bouchikh S, Stirnemann J, Prendki V, et al. Treatment duration of extra-pulmonary tuberculosis: 6 months or more? TB-INFO database analysis. Rev Med Interne. 2012;33:665–671.
  • Mendonca AMC, Kritski AL, Land MGP, et al. Abandonment of treatment for latent tuberculosis infection and socioeconomic factors in children and adolescents: Rio de Janeiro, Brazil. PLoS ONE. 2016;11:e0154843.
  • Mcgrath M, Gey Van Pittius NC, Van Helden PD, et al. Mutation rate and the emergence of drug resistance in Mycobacterium tuberculosis. J Antimicrob Chemoth. 2014;69:292–302.
  • Lauzardo M, Peloquin CA. Tuberculosis therapy for 2016 and beyond. Expert Opin Pharmacother. 2016;17:1859–1872.
  • Field SK. Bedaquiline for the treatment of multidrug-resistant tuberculosis: great promise or disappointment? Ther Adv Chronic Dis. 2015;6:170–184.
  • Xu J, Wang B, Hu M, et al. Primary clofazimine and bedaquiline resistance among isolates from patients with multidrug-resistant tuberculosis. Antimicrob Agents Chemother. 2017;61:e00239–17.
  • Manohar A, Ahuja J, Crane JK. Immunotherapy for infectious diseases: past, present, and future. Immunol Invest. 2015;44:731–737.
  • Abate G, Hoft DF. Immunotherapy for tuberculosis: future prospects. Immunotargets Ther. 2016;5:37–45.
  • Doherty TM. Immunotherapy for TB. Immunotherapy. 2012;4:629–647.
  • Harriff MJ, Cansler ME, Toren KG, et al. Human lung epithelial cells contain Mycobacterium tuberculosis in a late endosomal vacuole and are efficiently recognized by CD8+ T Cells. PLoS ONE. 2014;9:e97515.
  • Rothchild AC, Stowell B, Goyal G, et al. Role of granulocyte-macrophage colony-stimulating factor production by T cells during Mycobacterium tuberculosis infection. MBio. 2017;8:e01514–17.
  • Roberts LL, Robinson CM. Mycobacterium tuberculosis infection of human dendritic cells decreases integrin expression, adhesion and migration to chemokines. Immunology. 2013;141:39–51.
  • Khan N, Vidyarthi A, Pahari S, et al. Signaling through NOD-2 and TLR-4 bolsters the t cell priming capability of dendritic cells by inducing autophagy. Sci Rep. 2016;6:19084.
  • Carmona J, Cruz A, Moreira-Teixeira L, et al. Mycobacterium tuberculosis strains are differentially recognized by TLRs with an impact on the immune response. PLoS ONE. 2013;8:1–10.
  • Zhao X, Khan N, Gan H, et al. Bcl-xL mediates RIPK3-dependent necrosis in M. tuberculosis - infected macrophages. Mucosal Immunol. 2017;10:1553–1568.
  • Verrall AJ, Gm N, Alisjahbana B, et al. Early clearance of Mycobacterium tuberculosis: a new frontier in prevention. Immunology. 2014;141:506–513.
  • Roca FJ, Ramakrishnan L. TNF dually mediates resistance and susceptibility to mycobacteria via mitochondrial reactive oxygen species. Cell. 2013;153:521–534.
  • Cambier CJ, O’Leary SM, O’Sullivan MP, et al. Phenolic glycolipid facilitates mycobacterial escape from microbicidal tissue-resident macrophages. Immunity. 2017;47:552–565.
  • Gideon HP, Phuah JY, Myers AJ, et al. Variability in tuberculosis granuloma t cell responses exists, but a balance of pro- and anti-inflammatory cytokines is associated with sterilization. PLoS Pathog. 2015;11:e1004603.
  • Srivastava S, Ernst JD. Cutting edge: direct recognition of infected cells by CD4 T cells is required for control of intracellular Mycobacterium tuberculosis in vivo. J Immunol. 2013;191:1016–1020.
  • Slight SR, Rangel-Moreno J, Gopal R, et al. CXCR5 + T helper cells mediate protective immunity against tuberculosis. J Clin Invest. 2013;123:1–15.
  • Green AM, DiFazio R, Flynn JL. IFN-γ from CD4 T cells is essential for host survival and enhances CD8 T cell function during Mycobacterium tuberculosis infection. J Immunol. 2013;190:270–277.
  • Sakai S, Kauffman KD, Sallin MA, et al. CD4 T cell-derived IFN-γ plays a minimal role in control of pulmonary Mycobacterium tuberculosis infection and must be actively repressed by pd-1 to prevent Lethal Disease. PLoS Pathogens. 2016;12:e1005667.
  • Allie N, Grivennikov SI, Keeton R, et al. Prominent role for T cell-derived tumour necrosis factor for sustained control of Mycobacterium tuberculosis infection. Sci Rep. 2013;3:1809.
  • Rook GAW. Th2 cytokines in susceptibility to tuberculosis. Curr Mol Med. 2007;7:327–337.
  • Torrado E, Cooper AM. IL-17 and Th17 cells in tuberculosis. Cytokine Growth Factor Rev. 2010;21:455–462.
  • Nouailles G, Dorhoi A, Koch M, et al. CXCL5-secreting pulmonary epithelial cells drive destructive neutrophilic inflammation in tuberculosis. J Clin Invest. 2014;124:1268–1282.
  • Rivas-Santiago B, Sada E, Tsutsumi V, et al. β-Defensin gene expression during the course of experimental tuberculosis infection. J Infect Dis. 2006;194:697–701.
  • Castañeda-Delgado J, Hernández-Pando R, Serrano CJ, et al. Kinetics and cellular sources of cathelicidin during the course of experimental latent tuberculous infection and progressive pulmonary tuberculosis. Clin Exp Immunol. 2010;161:542–550.
  • Lai Y, Gallo RL. AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol. 2009;30:131–141.
  • Arranz-Trullén J, Lu L, Pulido D, et al. Host antimicrobial peptides: the promise of new treatment strategies against tuberculosis. Front Immunol. 2017;8:1499.
  • Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311:1770–1773.
  • Martineau AR, Wilkinson KA, Newton SM, et al. IFN-γ- and TNF-independent vitamin D-inducible human suppression of mycobacteria: the role of Cathelicidin LL-37. J Immunol. 2007;178:7190–7198.
  • Ralph AP, Waramori G, Pontororing GJ, et al. L-arginine and vitamin D adjunctive therapies in pulmonary tuberculosis: a randomised, double-blind, placebo-controlled trial. PLoS ONE. 2013;8:e70032.
  • Wejse C, Gomes VF, Rabna P, et al. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. Am J Resp Crit Care. 2009;179:843–850.
  • Martineau AR, Timms PM, Bothamley GH, et al. High-dose vitamin D3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet. 2011;377:242–250.
  • Daley P, Jagannathan V, John KR, et al. Adjunctive vitamin D for treatment of active tuberculosis in India: a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2015;15:528–534.
  • Wallis RS, Zumla A. Vitamin D as adjunctive host-directed therapy in tuberculosis: a systematic review. Open Forum Infect Dis. 2016;3:1–7.
  • Coussens AK, Wilkinson RJ, Martineau AR. Phenylbutyrate is bacteriostatic against Mycobacterium tuberculosis and regulates the macrophage response to infection, synergistically with 25-hydroxy-vitamin D3. PLoS Pathog. 2015;11:1–23.
  • Steinmann J, Halldórsson S, Agerberth B, et al. Phenylbutyrate induces antimicrobial peptide expression. Antimicrob Agents Chemother. 2009;53:5127–5133.
  • Fehlbaum P, Rao M, Zasloff M, et al. An essential amino acid induces epithelial β-defensin expression. Proc Natl Acad Sci USA. 2000;97:12723–12728.
  • Rivas-Santiago CE, Rivas-Santiago B, León DA, et al. Induction of β-defensins by l-isoleucine as novel immunotherapy in experimental murine tuberculosis. Clin Exp Immunol. 2011;164:80–89.
  • Rivas-Santiago B, Rivas Santiago CE, Sada E, et al. Prophylactic potential of defensins and L-isoleucine in tuberculosis household contacts: an experimental model. Immunotherapy. 2015;7:207–213.
  • Llamas-Gonzalez YY, Pedroza-Roldan C, Cortes-Serna MB, et al. The synthetic cathelicidin HHC-10 inhibits mycobacterium bovis BCG in vitro and in C57BL/6 mice. Microb Drug Resist. 2013;19:124–129.
  • Rivas-Santiago B, Castañeda-Delgado JE, Rivas Santiago CE, et al. Ability of innate defence regulator peptides idr-1002, idr-hh2 and idr-1018 to protect against Mycobacterium tuberculosis infections in animal models. PLoS ONE. 2013;8:e59119.
  • Rivas-Santiago B, Rivas Santiago CE, Castañeda-Delgado JE, et al. Activity of LL-37, CRAMP and antimicrobial peptide-derived compounds E2, E6 and CP26 against Mycobacterium tuberculosis. Int J Antimicrob Ag. 2013;41:143–148.
  • Silva JP, Gonçalves C, Costa C, et al. Delivery of LLKKK18 loaded into self-assembling hyaluronic acid nanogel for tuberculosis treatment. J Control Release. 2016;235:112–124.
  • Clifford V, Tebruegge M, Zufferey C, et al. Mycobacteria-specific cytokine responses as correlates of treatment response in active and latent tuberculosis. J Infect. 2017;75:132–145.
  • Tebruegge M, Dutta B, Donath S, et al. Mycobacteria-specific cytokine responses detect tuberculosis infection and distinguish latent from active tuberculosis. Am J Resp Crit Care. 2015;192:485–499.
  • Commins SP, Borish L, Steinke JW. Immunologic messenger molecules: cytokines, interferons, and chemokines. J Allergy Clin Immunol. 2010;125:S53–S72.
  • Denis M, Ghadirian E. Immunotherapy of airborne tuberculosis in mice via the lung-specific delivery of cytokines. Can J Infect Dis. 1993;4:38–42.
  • Reljic R. IFN-γ therapy of tuberculosis and related infections. J Interf Cytok Res. 2007;27:353–364.
  • Condos R, Rom WN, Schluger NW. Treatment of multidrug-resistant pulmonary tuberculosis with interferon-γ via aerosol. Lancet. 1997;349:1513–1515.
  • Gao X-F, Z-W Yang, Li J. Adjunctive therapy with interferon-gamma for the treatment of pulmonary tuberculosis: a systematic review. Int J Infect Dis. 2011;15:e594–e600.
  • Giosuè S, Casarini M, Alemanno L, et al. Effects of aerosolized interferon-α in patients with pulmonary tuberculosis. Am J Respir Crit Care Med. 1998;158:1156–1162.
  • Francisco-Cruz A, Aguilar-Santelises M, Ramos-Espinosa O, et al. Granulocyte-macrophage colony-stimulating factor: not just another haematopoietic growth factor. Med Oncol. 2014;31:774.
  • Berretta F, St-Pierre J, Piccirillo CA, et al. IL-2 contributes to maintaining a balance between CD4+foxp3+ regulatory t cells and effector CD4+ T cells required for immune control of blood-stage malaria infection. J Immunol. 2011;186:4862–4871.
  • Zhang YR, Liu J, Wang Y, et al. Immunotherapy using IL-2 and GM-CSF is a potential treatment for multidrug-resistant Mycobacterium tuberculosis. Sci China Life Sci. 2012;55:800–806.
  • Toossi Z, Kleinhenz ME, Ellner JJ. Defective interleukin 2 production and responsiveness in human pulmonary tuberculosis. J Exp Med. 1986;163:1162–1172.
  • Johnson BJ, Bekker L-G, Rickman R, et al. rhulL-2 adjunctive therapy in multidrug resistant tuberculosis: a comparison of two treatment regimens and placebo. Tuber Lung Dis. 1997;78:195–203.
  • Shen H, Min R, Tan Q, et al. The beneficial effects of adjunctive recombinant human interleukin-2 for multidrug resistant tuberculosis. Arch Med Sci. 2015;11:584–590.
  • Denis M, Gregg EO, Ghandirian E. Cytokine modulation of Mycobacterium tuberculosis growth in human macrophages. Int J Immunopharmacol. 1990;12:721–727.
  • Pedral-Sampaio DB, Netto EM, Brites C, et al. Use of Rhu-GM-CSF in pulmonary tuberculosis patients: results of a randomized clinical trial. Braz J Infect Dis. 2003;7:245–252.
  • Horn T, Burke P, Karp J, et al. Intravenous administration of recombinant human granulocyte-macrophage colony-stimulating factor causes a cutaneous eruption. Arch Dermatol. 1991;127:49–52.
  • Rutz S, Wang X, Ouyang W. The IL-20 subfamily of cytokines-from host defence to tissue homeostasis. Nat Rev Immunol. 2014;14:783–795.
  • Behrends J, Renauld JC, Ehlers S, et al. IL-22 is mainly produced by IFNγ-secreting cells but is dispensable for host protection against Mycobacterium tuberculosis infection. PLoS ONE. 2013;8:37–40.
  • Dhiman R, Periasamy S, Barnes PF, et al. NK1.1+ cells and IL-22 regulate vaccine-induced protective immunity against challenge with Mycobacterium tuberculosis. J Immunol. 2012;189:897–905.
  • Zeng G, Chen CY, Huang D, et al. Membrane-bound il-22 after de novo production in tuberculosis and anti-Mycobacterium tuberculosis effector function of IL-22+ CD4+ T Cells. J Immunol. 2011;187:190–199.
  • Ma Y, Chen HD, Wang Y, et al. Interleukin 24 as a novel potential cytokine immunotherapy for the treatment of Mycobacterium tuberculosis infection. Microbes Infect. 2011;13:1099–1110.
  • Mata-Espinosa DA, Mendoza-Rodríguez V, Aguilar-León D, et al. Therapeutic effect of recombinant adenovirus encoding interferon-γ in a murine model of progressive pulmonary tuberculosis. Mol Ther. 2008;16:1065–1072.
  • Francisco-Cruz A, Mata-Espinosa D, Ramos-Espinosa O, et al. Efficacy of gene-therapy based on adenovirus encoding granulocyte-macrophage colony-stimulating factor in drug-sensitive and drug-resistant experimental pulmonary tuberculosis. Tuberculosis. 2016;100:5–14.
  • Ramos-Espinosa O, Hernández-Bazán S, Francisco-Cruz A, et al. Gene therapy based in antimicrobial peptides and proinflammatory cytokine prevents reactivation of experimental latent tuberculosis. Pathog Dis. 2016;74:1–8.
  • Hernandez-Pando R, Orozco HE, Sampieri A, et al. Correlation between the kinetics of Th1, Th2 cells and pathology in a murine model of experimental pulmonary tuberculosis. Immunology. 1996;89:26–33.
  • Hernandez-Pando R, Orozco HE, Arriaga K, et al. Analysis of the local kinetics and localization of interleukin-lα, tumour necrosis factor-a and transforming growth factor-β, during the course of experimental pulmonary tuberculosis. Immunology. 1997;90:607–617.
  • Francisco-Cruz A, Mata-Espinosa D, Estrada-Parra S, et al. Immunotherapeutic effects of recombinant adenovirus encoding granulocyte-macrophage colony-stimulating factor in experimental pulmonary tuberculosis. Clin Exp Immunol. 2013;171:283–297.
  • Glatman-Freedman A. The role of antibodies against TB. In: Norazmi M-N, Acosta A, Sarmiento ME, editors. The art & science of tuberculosis vaccine development. 2nd ed. Selangor Darul Ehsan, Malaysia: Oxford Fajar Sdn Bhd; 2010. p. 238–273.
  • Teitelbaum R, Glatman-Freedman A, Chen B, et al. A mAb recognizing a surface antigen of Mycobacterium tuberculosis enhances host survival. Proc Natl Acad Sci USA. 1998;95:15688–15693.
  • Hamasur B, Haile M, Pawlowski A, et al. A mycobacterial lipoarabinomannan specific monoclonal antibody and its F (ab’)2 fragment prolong survival of mice infected with Mycobacterium tuberculosis. Clin Exp Immunol. 2004;138:30–38.
  • Williams A, Reljic R, Naylor I, et al. Passive protection with immunoglobulin A antibodies against tuberculous early infection of the lungs. Immunology. 2004;111:328–333.
  • López Y, Yero D, Falero-Diaz G, et al. Induction of a protective response with an IgA monoclonal antibody against Mycobacterium tuberculosis 16 kDa protein in a model of progressive pulmonary infection. Int J Med Microbiol. 2009;299:447–452.
  • Olivares N, León A, López Y, et al. The effect of the administration of human gamma globulins in a model of BCG infection in mice. Tuberculosis. 2006;86:268–272.
  • Stadlmann J, Pabst M, Altmann F. Analytical and functional aspects of antibody sialylation. J Clin Immunol. 2010;30:S15–S19.
  • Nimmerjahn F, Ravetch JV. Divergent immunoglobulin G subclass activity through selective Fc receptor binding. Science. 2005;310:1510–1512.
  • Parekh R, Isenberg D, Rook G, et al. A comparative analysis of disease-associated changes in the galactosylation of serum IgG. J Autoimmun. 1989;2:101–114.
  • McCulloch J, Zhang Y, Dawson M, et al. Glycosylation of lgG during potentially arthritogenic lentiviral infections. Rheumatol Int. 1995;14:243–248.
  • Rademacher TW, Williams P, Dwek RA. Agalactosyl glycoforms of IgG autoantibodies are pathogenic. Proc Natl Acad Sci USA. 1994;91:6123–6127.
  • Ferrara C, Grau S, Jager C, et al. Unique carbohydrate-carbohydrate interactions are required for high affinity binding between FcγRIII and antibodies lacking core fucose. Proc Natl Acad Sci USA. 2011;108:12669–12674.
  • Lu LL, Chung AW, Rosebrock T, et al. A functional role for antibodies in tuberculosis. Cell. 2016;167:433–443.
  • Olivares N, Marquina B, Mata-Espinoza D, et al. The protective effect of immunoglobulin in murine tuberculosis is dependent on IgG glycosylation. Pathog Dis. 2013;69:176–183.
  • Olivares N, Rodriguez Y, Zatarain-Barron ZL, et al. A significant therapeutic effect of immunoglobulins administered alone, or in combination with conventional chemotherapy, in experimental pulmonary tuberculosis caused by drug-sensitive or drug-resistant strains. Pathog Dis. 2017;75:1–8.
  • Buccheri S, Reljic R, Caccamo N, et al. IL-4 depletion enhances host resistance and passive IgA protection against tuberculosis infection in BALB/c mice. Eur J Immunol. 2007;37:729–737.
  • Beamer GL, Flaherty DK, Assogba BD, et al. Interleukin-10 promotes Mycobacterium tuberculosis disease progression in CBA/J mice. J Immunol. 2009;181:5545–5550.
  • Segueni N, Tritto E, Bourigault M, et al. Controlled Mycobacterium tuberculosis infection in mice under treatment with anti-IL-17A or IL-17F antibodies, in contrast to TNFα neutralization. Sci Rep. 2016;6:36923.
  • Shen L, Shi H, Gao Y, et al. The characteristic pro fi les of PD-1 and PD-L1 expressions and dynamic changes during treatment in active tuberculosis. Tuberculosis. 2016;101:146–150.
  • Singh A, Mohan A, Dey AB, et al. Inhibiting the programmed death 1 pathway rescues Mycobacterium tuberculosis – specific interferon γ – producing T cells from apoptosis in patients with pulmonary tuberculosis. J Infect Dis. 2013;208:603–615.
  • Toossi Z, Gogate P, Shiratsuchi H, et al. Enhanced production of TGF-β by blood monocytes from patients with active tuberculosis and presence of TGF-β in tuberculous granulomatous lung lesions. J Immunol. 1995;154:465–473.
  • Hernández-Pando R, Orozco-Esteves H, Maldonado H, et al. A combination of a transforming growth factor-β antagonist and an inhibitor of cyclooxygenase is an effective treatment for murine pulmonary tuberculosis. Clin Exp Immunol. 2006;144:264–272.
  • Stanford JL, Bahr GM, Rook GAW, et al. Immunotherapy with Mycobacterium vaccae as an adjunct to chemotherapy in the treatment of pulmonary tuberculosis. Tubercle. 1990;71:87–93.
  • Zuany-Amorim C, Sawicka E, Manlius C, et al. Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells. Nat Med. 2002;8:625–629.
  • Thaiss CA, Kaufmann SH. Toward novel vaccines against tuberculosis: current hopes and obstacles. Yale J Biol Med. 2010;83:209–215.
  • Dlugovitzky D, Fiorenza G, Farroni M, et al. Immunological consequences of three doses of heat-killed Mycobacterium vaccae in the immunotherapy of tuberculosis. Resp Med. 2006;100:1079–1087.
  • Dlugovitzky D, Notario R, Martinel-Lamas D, et al. Immunotherapy with oral, heat-killed, Mycobacterium vaccae in patients with moderate to advanced pulmonary tuberculosis. Immunotherapy. 2010;2:159–169.
  • Vilaplana C, Gil O, Cáceres N, et al. Prophylactic effect of a therapeutic vaccine against tb based on fragments of Mycobacterium tuberculosis. PLoS ONE. 2011;6:2–6.
  • Vilaplana C, Montané E, Pinto S, et al. Double-blind, randomized, placebo-controlled phase i clinical trial of the therapeutical antituberculous vaccine RUTI®. Vaccine. 2010;28:1106–1116.
  • Pj C. RUTI: A new chance to shorten the treatment of latent tuberculosis infection. Tuberculosis. 2006;86:273–289.
  • Nell AS, D’Lom E, Bouic P, et al. Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection. PLoS ONE. 2014;9:e89612.
  • Hernández-Pando R, Streber MDLL, Orozco H, et al. The effects of androstenediol and dehydroepiandrosterone on the course and cytokine profile of tuberculosis in BALB/c mice. Immunology. 1998;95:234–241.
  • Hernández-Pando R, De La Luz Streber M, Orozco H, et al. Emergent immunoregulatory properties of combined glucocorticoid and anti-glucocorticoid steroids in a model of tuberculosis. Q J Med. 1998;91:755–766.
  • Hernández-Pando R, Aguilar-Leon D, Orozco H, et al. 16α-Bromoepiandrosterone restores t helper cell type 1 activity and accelerates chemotherapy- induced bacterial clearance in a model of progressive pulmonary tuberculosis. J Infect Dis. 2005;191:299–306.
  • Stickney DR, Noveljic Z, Garsd A, et al. Safety and activity of the immune modulator HE2000 on the incidence of tuberculosis and other opportunistic infections in AIDS patients. Antimicrob Agents Chemother. 2007;51:2639–2641.
  • Reading C, Dowding C, Schramm B, et al. Improvement in immune parameters and human immunodeficiency virus-1 viral response in individuals treated with 16α-bromoepiandrosterone (HE2000). Clin Microbiol Infect. 2006;12:1082–1088.
  • Wang Y, Ke X, Khara JS, et al. Synthetic modifications of the immunomodulating peptide thymopentin to confer anti-mycobacterial activity. Biomaterials. 2014;35:3102–3109.
  • Yuan XL, Wen Q, De NM, et al. Immune formulation-assisted conventional therapy on anti-infective effectiveness of multidrug-resistant Mycobacterium tuberculosis infection mice. Asian Pac J Trop Med. 2016;9:293–297.
  • Parida SK, Madansein R, Singh N, et al. Cellular therapy in tuberculosis. Int J Infect Dis. 2015;32:32–38.
  • Yagi H, Soto-Gutierrez A, Parekkadan B, et al. Mesenchymal stem cells: mechanisms of immunomodulation and homing. Cell Transplant. 2010;19:667–679.
  • Duffy MM, Ritter T, Ceredig R, et al. Mesenchymal stem cell effects on T-cell effector pathways. Stem Cell Res Therapy. 2011;2:34.
  • Raghuvanshi S, Sharma P, Singh S, et al. Mycobacterium tuberculosis evades host immunity by recruiting mesenchymal stem cells. Proc Natl Acad Sci USA. 2010;107:21653–21658.
  • Khan A, Mann L, Papanna R, et al. Mesenchymal stem cells internalize Mycobacterium tuberculosis through scavenger receptors and restrict bacterial growth through autophagy. Sci Rep. 2017;7:1–15.
  • Skrahin A, Ahmed RK, Ferrara G, et al. Autologous mesenchymal stromal cell infusion as adjunct treatment in patients with multidrug and extensively drug-resistant tuberculosis: an open-label phase 1 safety trial. Lancet Respir Med. 2014;2:108–122.
  • Skrahin A, Jenkins HE, Hurevich H, et al. Effectiveness of a novel cellular therapy to treat multidrug-resistant tuberculosis. J Clin Tuberc Other Mycobact Dis. 2016;4:21–27.
  • Mesiano G, Todorovic M, Gammaitoni L, et al. Cytokine-induced killer (CIK) cells as feasible and effective adoptive immunotherapy for the treatment of solid tumors. Expert Opin Biol Ther. 2012;12:673–684.
  • Leemhuis T, Wells S, Scheffold C, et al. A phase I trial of autologous cytokine-induced killer cells for the treatment of relapsed Hodgkin disease and non-Hodgkin lymphoma. Biol Blood Marrow Transplant. 2005;11:181–187.
  • Ping X, Junchi X, Xinnian C, et al. Autologous cytokine-induced killer (CIK) immunotherapy in a case of disseminated tuberculosis. Sarcoidosis Vasc Diffuse. 2015;32:83–86.
  • Castillo EF, Dekonenko A, Arko-Mensah J, et al. Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation. Proc Natl Acad Sci USA. 2012;109:E3168–E3176.
  • Singh P, Subbian S. Harnessing the mTOR pathway for tuberculosis treatment. Front Microbiol. 2018;9:1–11.
  • Rao M, Valentini D, Zumla A, et al. Evaluation of the efficacy of valproic acid and suberoylanilide hydroxamic acid (vorinostat) in enhancing the effects of first-line tuberculosis drugs against intracellular Mycobacterium tuberculosis. Int J Infect Dis. 2018;69:78–84.
  • Gupta S, Cheung L, Pokkali S, et al. Suppressor cell-depleting immunotherapy with denileukin diftitox is an effective host-directed therapy for tuberculosis. J Infect Dis. 2017;215:1883–1887.

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