{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:12:43Z","timestamp":1790248363269,"version":"4.1.0"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:00:00Z","timestamp":1607299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Tuberculosis (TB) caused by <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (MTB) kills about 1.5 million people each year and the widely used Bacille Calmette-Gu\u00e9rin (BCG) vaccine\u00a0provides a partial protection against TB in children and adults. Because BCG vaccine evades lysosomal fusion in antigen presenting cells (APCs), leading to an inefficient production of peptides and antigen presentation required to activate CD4 T cells, we sought to boost its efficacy using novel agonists of RIG-I and NOD2 as adjuvants. We recently reported that the dinucleotide SB 9200 (Inarigivir) derived from our small molecule nucleic acid hybrid (SMNH)<jats:sup>\u00ae<\/jats:sup> platform, activated RIG-I and NOD2 receptors and exhibited a broad-spectrum antiviral activity against hepatitis B and C, Norovirus, RSV, influenza and parainfluenza. Inarigivir increased the ability of BCG-infected mouse APCs to secrete elevated levels of IL-12, TNF-\u03b1, and IFN-\u03b2, and Caspase-1 dependent IL-1\u03b2 cytokine. Inarigivir also increased the ability of macrophages to kill MTB in a Caspase-1-, and autophagy-dependent manner. Furthermore, Inarigivir led to a Capsase-1 and NOD2- dependent increase in the ability of BCG-infected APCs to present an Ag85B-p25 epitope to CD4 T cells <jats:italic>in vitro<\/jats:italic>. Consistent with an increase in immunogenicity of adjuvant treated APCs, the Inarigivir-BCG vaccine combination induced robust protection against tuberculosis in a mouse model of MTB infection, decreasing the lung burden of MTB by 1-log10 more than that afforded by BCG vaccine alone. The Inarigivir-BCG combination was also more efficacious than a muramyl-dipeptide-BCG vaccine combination against tuberculosis in mice, generating better memory T cell responses supporting its novel adjuvant potential for the BCG vaccine.<\/jats:p>","DOI":"10.3389\/fimmu.2020.592333","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T15:02:04Z","timestamp":1607353324000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["NOD2\/RIG-I Activating Inarigivir Adjuvant Enhances the Efficacy of BCG Vaccine Against Tuberculosis in Mice"],"prefix":"10.3389","volume":"11","author":[{"given":"Arshad","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vipul K.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Soudani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pearl","family":"Bakhru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dekai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Canaday","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjaneyulu","family":"Sheri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seetharamaiyer","family":"Padmanabhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreerupa","family":"Challa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radhakrishnan P.","family":"Iyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinnaswamy","family":"Jagannath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30654-6","article-title":"Global burden of tuberculosis: where we are and what to do","volume":"18","author":"Grobusch","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.04.00072604","article-title":"On the nature of Mycobacterium tuberculosis-latent bacilli","volume":"24","author":"Cardona","year":"2004","journal-title":"Eur Respir J"},{"key":"B3","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1111\/imr.12274","article-title":"T cells and adaptive immunity to Mycobacterium tuberculosis in humans","volume":"264","author":"Jasenosky","year":"2015","journal-title":"Immunol Rev"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/microbiolspec.TBTB2-0018-2016","article-title":"Cytokines and Chemokines in Mycobacterium tuberculosis Infection","volume":"4","author":"Domingo-Gonzalez","year":"2016","journal-title":"Microbiol Spectr"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3310\/hta17370","article-title":"Systematic review and meta-analysis of the current evidence on the duration of protection by bacillus Calmette\u2013Gu\u00e9rin vaccination against tuberculosis","volume":"17","author":"Abubakar","year":"2013","journal-title":"Heal Technol Assess"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit790","article-title":"Protection by BCG Vaccine Against Tuberculosis: A Systematic Review of Randomized Controlled Trials","volume":"58","author":"Mangtani","year":"2014","journal-title":"Clin Infect Dis"},{"key":"B7","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0041-3879(81)90037-4","article-title":"How environmental mycobacteria may predetermine the protective efficacy of BCG","volume":"62","author":"Stanford","year":"1981","journal-title":"Tubercle"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/0041-3879(81)90038-6","article-title":"The effect of two distinct forms of cell-mediated response to mycobacteria on the protective efficacy of BCG","volume":"62","author":"Rook","year":"1981","journal-title":"Tubercle"},{"key":"B9","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/trstmh\/tru168","article-title":"Trained immunity: consequences for the heterologous effects of BCG vaccination","volume":"109","author":"Kleinnijenhuis","year":"2015","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.11.011","article-title":"Immunometabolic Pathways in BCG-Induced Trained Immunity","volume":"17","author":"Arts","year":"2016","journal-title":"Cell Rep"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2008410117","article-title":"BCG vaccine protection from severe coronavirus disease 2019 (COVID-19)","volume":"117","author":"Escobar","year":"2020","journal-title":"Proc Natl Acad Sci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0337-y","article-title":"BCG-induced trained immunity: can it offer protection against COVID-19","volume":"20","author":"O\u2019Neill","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31025-4","article-title":"Considering BCG vaccination to reduce the impact of COVID-19","volume":"395","author":"Curtis","year":"2020","journal-title":"Lancet"},{"key":"B14","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nri.2017.54","article-title":"Unique aspects of the perinatal immune system","volume":"17","author":"Zhang","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2017.00407","article-title":"Immune Responses to Bacillus Calmette\u2013Gu\u00e9rin Vaccination: Why Do They Fail to Protect against Mycobacterium tuberculosis","volume":"8","author":"Moliva","year":"2017","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2016.05.011","article-title":"Complement factor H interferes with Mycobacterium bovis BCG entry into macrophages and modulates the pro-inflammatory cytokine response","volume":"221","author":"Abdul-Aziz","year":"2016","journal-title":"Immunobiology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/s41541-019-0122-8","article-title":"An autophagy-inducing and TLR-2 activating BCG vaccine induces a robust protection against tuberculosis in mice","volume":"4","author":"Khan","year":"2019","journal-title":"NPJ Vaccines"},{"key":"B18","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S0034-5687(01)00261-4","article-title":"The role of immunity in susceptibility to respiratory infection in the aging lung","volume":"128","author":"Meyer","year":"2001","journal-title":"Respir Physiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/854507","article-title":"Th1 and Th17 Cells in Tuberculosis: Protection, Pathology, and Biomarkers","volume":"2015","author":"Lyadova","year":"2015","journal-title":"Mediators Inflammation"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-100019","article-title":"Kolls JK. T cell-mediated host immune defenses in the lung","volume":"31","author":"Chen","year":"2013","journal-title":"Annu Rev Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.5.3250","article-title":"Processing and Presentation of a Mycobacterial Antigen 85B Epitope by Murine Macrophages Is Dependent on the Phagosomal Acquisition of Vacuolar Proton ATPase and In Situ Activation of Cathepsin D","volume":"177","author":"Singh","year":"2006","journal-title":"J Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100521","article-title":"Cutting edge: Nicastrin and related components of \u03b3-secretase generate a peptide epitope facilitating immune recognition of intracellular mycobacteria, through MHC class II-dependent priming of T cells","volume":"187","author":"Singh","year":"2011","journal-title":"J Immunol"},{"key":"B23","first-page":"35","article-title":"\u201cChapter 4 - Increased Immunogenicity Through Autophagy,\u201d","volume-title":"Immunology","author":"Jagannath","year":"2008"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1126\/science.8098550","article-title":"Sequestration from immune CD4+ T cells of mycobacteria growing in human macrophages","volume":"260","author":"Pancholi","year":"1993","journal-title":"Sci (80 )"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409716102","article-title":"Mechanism of phagolysosome biogenesis block by viable Mycobacterium tuberculosis","volume":"102","author":"Vergne","year":"2005","journal-title":"Proc Natl Acad Sci"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1928","article-title":"Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells","volume":"15","author":"Jagannath","year":"2009","journal-title":"Nat Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines3020320","article-title":"Vaccine Adjuvants: from 1920 to 2015 and Beyond","volume":"3","author":"Pasquale","year":"2015","journal-title":"Vaccines"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081779","article-title":"Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide","volume":"206","author":"Coulombe","year":"2009","journal-title":"J Exp Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2014.11.015","article-title":"Freund\u2019s adjuvant, NOD2 and mycobacteria","volume":"23","author":"Behr","year":"2015","journal-title":"Curr Opin Microbiol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s00281-007-0083-2","article-title":"The Nodosome: Nod1 and Nod2 control bacterial infections and inflammation","volume":"29","author":"Tattoli","year":"2007","journal-title":"Semin Immunopathol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01544.x","article-title":"NOD2 controls the nature of the inflammatory response and subsequent fate of Mycobacterium tuberculosis and M. bovis BCG in human macrophages","volume":"13","author":"Brooks","year":"2011","journal-title":"Cell Microbiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nature13133","article-title":"Endosomes are specialized platforms for bacterial sensing and NOD2 signalling","volume":"509","author":"Nakamura","year":"2014","journal-title":"Nature"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1202870109","article-title":"Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes","volume":"109","author":"Kleinnijenhuis","year":"2012","journal-title":"Proc Natl Acad Sci"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/5812743","article-title":"BCG-Induced Trained Immunity in Healthy Individuals: The Effect of Plasma Muramyl Dipeptide Concentrations","volume":"2020","author":"Mourits","year":"2020","journal-title":"J Immunol Res"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/vaccines8010067","article-title":"RNA Sensing of Mycobacterium tuberculosis and Its Impact on TB Vaccination Strategies","volume":"8","author":"Burkert","year":"2020","journal-title":"Vaccines"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.05.004","article-title":"The Cytosolic Sensor cGAS Detects Mycobacterium tuberculosis DNA to Induce Type I Interferons and Activate Autophagy","volume":"17","author":"Watson","year":"2015","journal-title":"Cell Host Microbe"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.05.017","article-title":"Mycobacterium tuberculosis Meets the Cytosol: The Role of cGAS in Anti-mycobacterial Immunity","volume":"17","author":"Majlessi","year":"2015","journal-title":"Cell Host Microbe"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.24809","article-title":"SB 9200, a novel agonist of innate immunity, shows potent antiviral activity against resistant HCV variants","volume":"89","author":"Jones","year":"2017","journal-title":"J Med Virol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e0169631","DOI":"10.1371\/journal.pone.0169631","article-title":"Antiviral Efficacy and Host Immune Response Induction during Sequential Treatment with SB 9200 Followed by Entecavir in Woodchucks","volume":"12","author":"Suresh","year":"2017","journal-title":"PloS One"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.044446","article-title":"Metabolism, Pharmacokinetics, Tissue Distribution, and Stability Studies of the Prodrug Analog of an Anti-Hepatitis B Virus Dinucleoside Phosphorothioate","volume":"40","author":"Coughlin","year":"2012","journal-title":"Drug Metab Dispos"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.10.1421","article-title":"Processing of Mycobacterium tuberculosis Antigen 85B Involves Intraphagosomal Formation of Peptide\u2013Major Histocompatibility Complex II Complexes and Is Inhibited by Live Bacilli that Decrease Phagosome Maturation","volume":"194","author":"Ramachandra","year":"2001","journal-title":"J Exp Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.1999.00026.x","article-title":"Phagocytic processing of antigens for presentation by class II major histocompatibility complex molecules","volume":"1","author":"Ramachandra","year":"1999","journal-title":"Cell Microbiol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00328","article-title":"NOD1 and NOD2 Signaling in Infection and Inflammation","volume":"3","author":"Moreira","year":"2012","journal-title":"Front Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2016-0375TR","article-title":"The Role of Nucleotide-Binding Oligomerization Domain-Like Receptors in Pulmonary Infection","volume":"57","author":"Wiese","year":"2017","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1615\/critrevimmunol.v30.i5.50","article-title":"Inflammasomes and their activation","volume":"30","author":"Khare","year":"2010","journal-title":"Crit Rev Immunol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/s41421-020-0167-x","article-title":"Inflammasome activation and regulation: toward a better understanding of complex mechanisms","volume":"6","author":"Zheng","year":"2020","journal-title":"Cell Discovery"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.05.003","article-title":"Immune signaling by RIG-I-like receptors","volume":"34","author":"Loo","year":"2011","journal-title":"Immunity"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.05.022","article-title":"Toll-like receptor 4 is a sensor for autophagy associated with innate immunity","volume":"27","author":"Xu","year":"2007","journal-title":"Immunity"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201142105","article-title":"NOD2 enhances the innate response of alveolar macrophages to Mycobacterium tuberculosis in humans","volume":"42","author":"Ju\u00e1rez","year":"2012","journal-title":"Eur J Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141548","article-title":"Activation of the NLRP3 inflammasome by Mycobacterium tuberculosis is uncoupled from susceptibility to active tuberculosis","volume":"42","author":"Dorhoi","year":"2012","journal-title":"Eur J Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2010.06.002","article-title":"The Achilles heel of BCG","volume":"90","author":"Orme","year":"2010","journal-title":"Tuberculosis"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2018.00461","article-title":"Trying to See the Forest through the Trees: Deciphering the Nature of Memory Immunity to Mycobacterium tuberculosis","volume":"9","author":"Orme","year":"2018","journal-title":"Front Immunol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"e13045","DOI":"10.2196\/13045","article-title":"Stimulation of Nucleotide Oligomerization Domain and Toll-Like Receptors 2 to Enhance the Effect of Bacillus Calmette Guerin Immunization for Prevention of Mycobacterium Tuberculosis Infection: Protocol for a Series of Preclinical Randomized Controlled Tr","volume":"8","author":"Eisenhut","year":"2019","journal-title":"JMIR Res Protoc"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.4.2714-2717.2001","article-title":"Boosting Vaccine for Tuberculosis","volume":"69","author":"Brooks","year":"2001","journal-title":"Infect Immun"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxq053","article-title":"Early events governing memory CD8+ T-cell differentiation","volume":"22","author":"Obar","year":"2010","journal-title":"Int Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.05126.x","article-title":"Memory CD8+ T cell differentiation","volume":"1183","author":"Obar","year":"2010","journal-title":"Ann N Y Acad Sci"},{"key":"B57","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.smim.2016.02.001","article-title":"Role of memory T cell subsets for adoptive immunotherapy","volume":"28","author":"Busch","year":"2016","journal-title":"Semin Immunol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2019.01317","article-title":"The Humoral Immune Response to BCG Vaccination","volume":"10","author":"Tanner","year":"2019","journal-title":"Front Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-8-9","article-title":"Persistence of the immune response induced by BCG vaccination","volume":"8","author":"Weir","year":"2008","journal-title":"BMC Infect Dis"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2009.09.002","article-title":"Neonatal immunity: faulty T-helpers and the shortcomings of dendritic cells","volume":"30","author":"Zaghouani","year":"2009","journal-title":"Trends Immunol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2018.00532","article-title":"Neonatal Immunization: Rationale, Current State, and Future Prospects","volume":"9","author":"Whittaker","year":"2018","journal-title":"Front Immunol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/nri3247","article-title":"Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination","volume":"12","author":"Desmet","year":"2012","journal-title":"Nat Rev Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-7915.2011.00306.x","article-title":"Cyclic di-nucleotides: new era for small molecules as adjuvants","volume":"5","author":"Libanova","year":"2012","journal-title":"Microb Biotechnol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2018.05.003","article-title":"Combination and inducible adjuvants targeting nucleic acid sensors","volume":"41","author":"Temizoz","year":"2018","journal-title":"Curr Opin Pharmacol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-019-0333-0","article-title":"STING signaling and host defense against microbial infection","volume":"51","author":"Ahn","year":"2019","journal-title":"Exp Mol Med"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.08.007","article-title":"Type I Interferons in Host Defense","volume":"25","author":"Stetson","year":"2006","journal-title":"Immunity"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2017\/8796760","article-title":"IFN- \u03b1 Boosting of Mycobacterium bovis Bacillus Calmette G\u00fcerin-Vaccine Promoted Th1 Type Cellular Response and Protection against M. tuberculosis Infection","volume":"2017","author":"Rivas-Santiago","year":"2017","journal-title":"BioMed Res Int"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0908583","article-title":"IFN-\u03b2 improves BCG immunogenicity by acting on DC maturation","volume":"85","author":"Giacomini","year":"2009","journal-title":"J Leukoc Biol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.02.057","article-title":"Recombinant BCG Expressing ESX-1 of Mycobacterium marinum Combines Low Virulence with Cytosolic Immune Signaling and Improved TB Protection","volume":"18","author":"Gr\u00f6schel","year":"2017","journal-title":"Cell Rep"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2019.00958","article-title":"NOD2 and TLR2 Signal via TBK1 and PI31 to Direct Cross-Presentation and CD8 T Cell Responses","volume":"10","author":"Corridoni","year":"2019","journal-title":"Front Immunol"},{"key":"B71","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.molimm.2017.11.028","article-title":"Innate immune receptors for cross-presentation: The expanding role of NLRs","volume":"113","author":"Corridoni","year":"2019","journal-title":"Mol Immunol"},{"key":"B72","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.cellimm.2008.07.002","article-title":"Mycobacterium bovis BCG decreases MHC-II expression in vivo on murine lung macrophages and dendritic cells during aerosol infection","volume":"254","author":"Pecora","year":"2009","journal-title":"Cell Immunol"},{"key":"B73","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.cellimm.2013.11.007","article-title":"BCG vaccine mediated reduction in the MHC-II expression of macrophages and dendritic cells is reversed by activation of Toll-like receptors 7 and 9","volume":"287","author":"Bakhru","year":"2014","journal-title":"Cell Immunol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2069","article-title":"NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation","volume":"16","author":"Cooney","year":"2010","journal-title":"Nat Med"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2595","article-title":"Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function","volume":"14","author":"Sokolovska","year":"2013","journal-title":"Nat Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.592333\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T15:02:08Z","timestamp":1607353328000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.592333\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,7]]},"references-count":75,"alternative-id":["10.3389\/fimmu.2020.592333"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.592333","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,7]]},"article-number":"592333"}}