{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T19:53:09Z","timestamp":1787601189910,"version":"build-2736575974"},"reference-count":65,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ANPCyT\u2013FONCyT Argentina","award":["Grant PICT-2016-0410"],"award-info":[{"award-number":["Grant PICT-2016-0410"]}]},{"name":"JSPS Japan","award":["(A) (19H00965)"],"award-info":[{"award-number":["(A) (19H00965)"]}]},{"name":"NARO Bio-oriented Technology Research Advancement Institution","award":["No. 01002A"],"award-info":[{"award-number":["No. 01002A"]}]},{"name":"\u201cScientific Research on Innovative Areas\u201d from the Ministry of Education, Culture, Sports, Science and Technology (MEXT)","award":["16H06429, 16K21723, and 16H06435"],"award-info":[{"award-number":["16H06429, 16K21723, and 16H06435"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The nasal priming with nonviable Lactobacillus rhamnosus CRL1505 (NV1505) or its purified peptidoglycan (PG1505) differentially modulates the respiratory innate immune response in infant mice, improving their resistance to primary respiratory syncytial virus (RSV) infection and secondary pneumococcal pneumonia. In association with the protection against RSV-pneumococcal superinfection, it was found that NV1505 or PG1505 significantly enhance the numbers of CD11c+SiglecF+ alveolar macrophages (AMs) producing interferon (IFN)-\u03b2. In this work, we aimed to further advance in the characterization of the beneficial effects of NV1505 and PG1505 in the context of a respiratory superinfection by evaluating whether their immunomodulatory properties are dependent on AM functions. Macrophage depletion experiments and a detailed study of their production of cytokines and antiviral factors clearly demonstrated the key role of this immune cell population in the improvement of both the reduction of pathogens loads and the protection against lung tissue damage induced by the immunobiotic CRL1505 strain. Studies at basal conditions during primary RSV or S. pneumoniae infections, as well as during secondary pneumococcal pneumonia, brought the following five notable findings regarding the immunomodulatory effects of NV1505 and PG1505: (a) AMs play a key role in the beneficial modulation of the respiratory innate immune response and protection against RSV infection, (b) AMs are necessary for improved protection against primary and secondary pneumococcal pneumonia, (c) the generation of activated\/trained AMs would be essential for the enhanced protection against respiratory pathogens, (d) other immune and nonimmune cell populations in the respiratory tract may contribute to the protection against bacterial and viral infections, and (e) the immunomodulatory properties of NV1505 and PG1505 are strain-specific. These findings significantly improve our knowledge about the immunological mechanisms involved in the modulation of respiratory immunity induced by beneficial microbes.<\/jats:p>","DOI":"10.3390\/cells9071653","type":"journal-article","created":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T09:45:31Z","timestamp":1594374331000},"page":"1653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["The Role of Alveolar Macrophages in the Improved Protection against Respiratory Syncytial Virus and Pneumococcal Superinfection Induced by the Peptidoglycan of Lactobacillus rhamnosus CRL1505"],"prefix":"10.3390","volume":"9","author":[{"given":"Patricia","family":"Clua","sequence":"first","affiliation":[{"name":"Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli, (CERELA-CONICET), Tucuman 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikado","family":"Tomokiyo","sequence":"additional","affiliation":[{"name":"Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"},{"name":"Livestock Immunology Unit, International Education and Research Center for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Raya Tonetti","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli, (CERELA-CONICET), Tucuman 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1979-9652","authenticated-orcid":false,"given":"Md. Aminul","family":"Islam","sequence":"additional","affiliation":[{"name":"Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"},{"name":"Livestock Immunology Unit, International Education and Research Center for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Garc\u00eda Castillo","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli, (CERELA-CONICET), Tucuman 4000, Argentina"},{"name":"Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Marcial","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli, (CERELA-CONICET), Tucuman 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Salva","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli, (CERELA-CONICET), Tucuman 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9683-0337","authenticated-orcid":false,"given":"Susana","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli, (CERELA-CONICET), Tucuman 4000, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5398-1867","authenticated-orcid":false,"given":"Hideki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Laboratory of Plant Pathology, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"},{"name":"Plant Immunology Unit, International Education and Research Center for Food Agricultural Immunology, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0301-872X","authenticated-orcid":false,"given":"Shoichiro","family":"Kurata","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruki","family":"Kitazawa","sequence":"additional","affiliation":[{"name":"Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"},{"name":"Livestock Immunology Unit, International Education and Research Center for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4941-4960","authenticated-orcid":false,"given":"Julio","family":"Villena","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli, (CERELA-CONICET), Tucuman 4000, Argentina"},{"name":"Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.3201\/eid1907.121625","article-title":"Influence of pneumococcal vaccines and respiratory syncytial virus on alveolar pneumonia, Israel","volume":"19","author":"Alonso","year":"2013","journal-title":"Emer. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Cebey-Lopez, M., Pardo-Seco, J., Gomez-Carballa, A., Martinon-Torres, N., Martinon-Sanchez, J.M., Justicia-Grande, A., Rivero-Calle, I., Pinnock, E., Salas, A., and Fink, C. (2016). Bacteremia in children hospitalized with respiratory syncytial virus infection. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146599"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bosch, A.A., Biesbroek, G., Trzcinski, K., Sanders, E.A., and Bogaert, D. (2013). Viral and bacterial interactions in the upper respiratory tract. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003057"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1016\/S0140-6736(12)60560-1","article-title":"Global, regional, and national causes of child mortality: An updated systematic analysis for 2010 with time trends since 2000","volume":"379","author":"Liu","year":"2012","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1378\/chest.12-1861","article-title":"The occurrence and impact of bacterial organisms complicating critical care illness associated with 2009 influenza A(H1N1) infection","volume":"144","author":"Muscedere","year":"2013","journal-title":"Chest"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1164\/rccm.201311-2110OC","article-title":"Respiratory syncytial virus increases the virulence of Streptococcus pneumoniae by binding to penicillin binding protein 1a. A new paradigm in respiratory infection","volume":"190","author":"Smith","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1128\/JVI.80.4.1629-1636.2006","article-title":"Respiratory viruses augment the adhesion of bacterial pathogens to respiratory epithelium in a viral species-and cell type-dependent manner","volume":"80","author":"Avadhanula","year":"2006","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1099\/jmm.0.47086-0","article-title":"Nontypeable Haemophilus influenzae and Streptococcus pneumoniae bind respiratory syncytial virus glycoprotein","volume":"56","author":"Avadhanula","year":"2007","journal-title":"J. Med. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1203\/01.pdr.0000188699.55279.1b","article-title":"Direct binding of respiratory syncytial virus to pneumococci: A phenomenon that enhances both pneumococcal adherence to human epithelial cells and pneumococcal invasiveness in a murine model","volume":"58","author":"Hament","year":"2005","journal-title":"Pediatr. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.3389\/fimmu.2017.01643","article-title":"Functional impairment of mononuclear phagocyte system by the human respiratory syncytial virus","volume":"8","author":"Bohmwald","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1165\/rcmb.2013-0414OC","article-title":"Alveolar macrophages contribute to the pathogenesis of human metapneumovirus infection while protecting against respiratory syncytial virus infection","volume":"51","author":"Kolli","year":"2014","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1046\/j.1365-2249.1996.d01-874.x","article-title":"Respiratory syncytial virus-induced cytokine production by neonatal macrophages","volume":"106","author":"Tsutsumi","year":"1996","journal-title":"Clin. Exp. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1183\/09031936.01.17203210","article-title":"IFN-gamma response and IL-8 plasma levels in neonates with respiratory syncytial virus bronchiolitis","volume":"17","author":"Schultz","year":"2001","journal-title":"Eur. Respir. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s12931-015-0282-7","article-title":"Alveolar macrophages support interferon gamma-mediated viral clearance in RSV-infected neonatal mice","volume":"16","author":"Eichinger","year":"2015","journal-title":"Respir. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1128\/JVI.02620-13","article-title":"Delayed sequelae of neonatal respiratory syncytial virus infection are dependent on cells of the innate immune system","volume":"88","author":"Harker","year":"2014","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cooper, G.E., Pounce, Z.C., Wallington, J.C., Bastidas-Legarda, L.Y., Nicholas, B., Chidomere, C., Robinson, E.C., Martin, K., Tocheva, A.S., and Christodoulides, M. (2016). Viral inhibition of bacterial phagocytosis by human macrophages: Redundant role of CD36. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163889"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"948","DOI":"10.3389\/fimmu.2017.00948","article-title":"Peptidoglycan from immunobiotic lactobacillus rhamnosus improves resistance of infant mice to respiratory syncytial viral infection and secondary pneumococcal pneumonia","volume":"8","author":"Clua","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.intimp.2015.02.006","article-title":"Non-viable immunobiotic Lactobacillus rhamnosus CRL1505 and its peptidoglycan improve systemic and respiratory innate immune response during recovery of immunocompromised-malnourished mice","volume":"25","author":"Kolling","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tomosada, Y., Chiba, E., Zelaya, H., Takahashi, T., Tsukida, K., Kitazawa, H., Alvarez, S., and Villena, J. (2013). Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection. BMC Immunol., 14.","DOI":"10.1186\/1471-2172-14-40"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Villena, J., Chiba, E., Tomosada, Y., Salva, S., Marranzino, G., Kitazawa, H., and Alvarez, S. (2012). Orally administered Lactobacillus rhamnosus modulates the respiratory immune response triggered by the viral pathogen-associated molecular pattern poly(I:C). BMC Immunol., 13.","DOI":"10.1186\/1471-2172-13-53"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.intimp.2013.06.024","article-title":"Immunobiotic Lactobacillus rhamnosus improves resistance of infant mice against respiratory syncytial virus infection","volume":"17","author":"Chiba","year":"2013","journal-title":"Int. Immunopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.3389\/fmicb.2017.01613","article-title":"Respiratory commensal bacteria corynebacterium pseudodiphtheriticum improves resistance of infant mice to respiratory syncytial virus and Streptococcus pneumoniae superinfection","volume":"8","author":"Kanmani","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1128\/IAI.00411-16","article-title":"Murine alveolar macrophages are highly susceptible to replication of coxiella burnetii phase II in vitro","volume":"84","author":"Fernandes","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1086\/344644","article-title":"Respiratory syncytial virus-induced activation of nuclear factor-kappaB in the lung involves alveolar macrophages and toll-like receptor 4-dependent pathways","volume":"186","author":"Haeberle","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1016\/j.cell.2018.09.042","article-title":"Induction of autonomous memory alveolar macrophages requires T cell help and is critical to trained immunity","volume":"175","author":"Yao","year":"2018","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cellimm.2018.01.005","article-title":"Alveolar macrophages","volume":"330","author":"Joshi","year":"2018","journal-title":"Cell. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.immuni.2013.05.007","article-title":"Cytosolic sensing of viruses","volume":"38","author":"Goubau","year":"2013","journal-title":"Immunity"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1086\/593173","article-title":"Macrophage impairment underlies airway occlusion in primary respiratory syncytial virus bronchiolitis","volume":"198","author":"Reed","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1084\/jem.20140825","article-title":"Alveolar macrophage-derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes","volume":"212","author":"Goritzka","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/nature12862","article-title":"Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity","volume":"505","author":"Schoggins","year":"2014","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14222","DOI":"10.1128\/JVI.01763-14","article-title":"The 2\u2032-5\u2032-oligoadenylate synthetase 3 enzyme potently synthesizes the 2\u2032-5\u2032-oligoadenylates required for RNase L activation","volume":"88","author":"Ibsen","year":"2014","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1089\/104303402760293547","article-title":"Adenovirus-mediated interferon gamma gene therapy for allergic asthma: Involvement of interleukin 12 and STAT4 signaling","volume":"13","author":"Behera","year":"2002","journal-title":"Hum. Gene Ther."},{"key":"ref_33","first-page":"589","article-title":"Nasal priming with immunobiotic Lactobacillus rhamnosus modulates inflammation-coagulation interactions and reduces influenza virus-associated pulmonary damage","volume":"64","author":"Zelaya","year":"2015","journal-title":"Inflamm. Res. Off. J. Eur.\/Histamine Res. Soc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"819","DOI":"10.3389\/fimmu.2017.00819","article-title":"Transient depletion of CD169(+) cells contributes to impaired early protection and effector CD8(+) T cell recruitment against mucosal respiratory syncytial virus infection","volume":"8","author":"Oh","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4441","DOI":"10.1128\/JVI.02541-07","article-title":"Alveolar macrophages are a major determinant of early responses to viral lung infection but do not influence subsequent disease development","volume":"82","author":"Pribul","year":"2008","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.3389\/fimmu.2018.01777","article-title":"Alveolar Macrophages in the resolution of inflammation, tissue repair, and tolerance to infection","volume":"9","author":"Allard","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Pyle, C.J., Uwadiae, F.I., Swieboda, D.P., and Harker, J.A. (2017). Early IL-6 signalling promotes IL-27 dependent maturation of regulatory T cells in the lungs and resolution of viral immunopathology. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006640"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1084\/jem.20121849","article-title":"Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance","volume":"210","author":"Soroosh","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/nri1648","article-title":"New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions","volume":"5","author":"Hunter","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/j.ajpath.2014.02.004","article-title":"IL-27R-mediated regulation of IL-17 controls the development of respiratory syncytial virus-associated pathogenesis","volume":"184","author":"Demoor","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Liu, F.D., Kenngott, E.E., Schroter, M.F., Kuhl, A., Jennrich, S., Watzlawick, R., Hoffmann, U., Wolff, T., Norley, S., and Scheffold, A. (2014). Timed action of IL-27 protects from immunopathology while preserving defense in influenza. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004110"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.smim.2011.08.003","article-title":"Induction of regulatory Tr1 cells and inhibition of T(H)17 cells by IL-27","volume":"23","author":"Pot","year":"2011","journal-title":"Semin. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1038\/ni1537","article-title":"Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10","volume":"8","author":"Stumhofer","year":"2007","journal-title":"Nat. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.imlet.2008.01.011","article-title":"Advances in understanding the anti-inflammatory properties of IL-27","volume":"117","author":"Stumhofer","year":"2008","journal-title":"Immunol. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1002\/eji.201546201","article-title":"Type I interferon promotes alveolar epithelial type II cell survival during pulmonary Streptococcus pneumoniae infection and sterile lung injury in mice","volume":"46","author":"Maier","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1128\/IAI.01572-14","article-title":"Type I interferon signaling regulates activation of the absent in melanoma 2 inflammasome during Streptococcus pneumoniae infection","volume":"82","author":"Fang","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"811","DOI":"10.4049\/jimmunol.1004143","article-title":"Streptococcus pneumoniae stimulates a STING-and IFN regulatory factor 3-dependent type I IFN production in macrophages, which regulates RANTES production in macrophages, cocultured alveolar epithelial cells, and mouse lungs","volume":"188","author":"Koppe","year":"2012","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"LeMessurier, K.S., Hacker, H., Chi, L., Tuomanen, E., and Redecke, V. (2013). Type I interferon protects against pneumococcal invasive disease by inhibiting bacterial transmigration across the lung. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003727"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1165\/rcmb.2013-0316OC","article-title":"Mechanisms of interferon-gamma production by neutrophils and its function during Streptococcus pneumoniae pneumonia","volume":"52","author":"Gomez","year":"2015","journal-title":"Am. J. of Respir. Cell Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.imbio.2011.10.012","article-title":"Protection against Streptococcus pneumoniae serotype 1 acute infection shows a signature of Th17-and IFN-gamma-mediated immunity","volume":"217","author":"Marques","year":"2012","journal-title":"Immunobiology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1164\/rccm.200207-698OC","article-title":"Alveolar macrophages have a protective antiinflammatory role during murine pneumococcal pneumonia","volume":"167","author":"Knapp","year":"2003","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.4049\/jimmunol.1002194","article-title":"Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice","volume":"186","author":"Kudva","year":"2011","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1172\/JCI57762","article-title":"Synergistic stimulation of type I interferons during influenza virus coinfection promotes Streptococcus pneumoniae colonization in mice","volume":"121","author":"Nakamura","year":"2011","journal-title":"J. Clinic. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/nm1765","article-title":"Inhibition of pulmonary antibacterial defense by interferon-gamma during recovery from influenza infection","volume":"14","author":"Sun","year":"2008","journal-title":"Nat. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/emmm.201302890","article-title":"Activation of IL-27 signalling promotes development of postinfluenza pneumococcal pneumonia","volume":"6","author":"Cao","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"E9162","DOI":"10.1073\/pnas.1720930115","article-title":"Interferon stimulation creates chromatin marks and establishes transcriptional memory","volume":"115","author":"Kamada","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Leopold Wager, C.M., Hole, C.R., Campuzano, A., Castro-Lopez, N., Cai, H., Caballero Van Dyke, M.C., Wozniak, K.L., Wang, Y., and Wormley, F.L. (2018). IFN-gamma immune priming of macrophages in vivo induces prolonged STAT1 binding and protection against Cryptococcus neoformans. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007358"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"543","DOI":"10.3389\/fimmu.2020.00543","article-title":"Efficient selection of new immunobiotic strains with antiviral effects in local and distal mucosal sites by using porcine intestinal epitheliocytes","volume":"11","author":"Albarracin","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3389\/fimmu.2017.00057","article-title":"Transcriptomic analysis of the innate antiviral immune response in porcine intestinal epithelial cells: Influence of immunobiotic Lactobacilli","volume":"8","author":"Albarracin","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nri3210","article-title":"Interferon-inducible effector mechanisms in cell-autonomous immunity","volume":"12","author":"MacMicking","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"633","DOI":"10.3389\/fimmu.2016.00633","article-title":"Respiratory antiviral immunity and immunobiotics: Beneficial effects on inflammation-coagulation interaction during influenza virus infection","volume":"7","author":"Zelaya","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1165\/rcmb.2011-0070OC","article-title":"Mouse lung CD103+ and CD11bhigh dendritic cells preferentially induce distinct CD4+ T-cell responses","volume":"46","author":"Furuhashi","year":"2012","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Kolling, Y., Salva, S., Villena, J., and Alvarez, S. (2018). Are the immunomodulatory properties of Lactobacillus rhamnosus CRL1505 peptidoglycan common for all Lactobacilli during respiratory infection in malnourished mice?. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194034"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.4049\/jimmunol.1001751","article-title":"Lactobacillus\u2014mediated priming of the respiratory mucosa protects against lethal pneumovirus infection","volume":"186","author":"Gabryszewski","year":"2011","journal-title":"J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.antiviral.2012.12.022","article-title":"Lactobacillus priming of the respiratory tract: Heterologous immunity and protection against lethal pneumovirus infection","volume":"97","author":"Chan","year":"2013","journal-title":"Antiviral Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/7\/1653\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:49:31Z","timestamp":1760176171000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/7\/1653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,9]]},"references-count":65,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["cells9071653"],"URL":"https:\/\/doi.org\/10.3390\/cells9071653","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,9]]}}}