1. de Heredia FP, Gómez-Martínez S, Marcos A. Obesity, inflammation and the immune system. Proc Nutr Soc. (2012) 71:332–8. doi: 10.1017/ s0029665112000092
2. Rytter MJH, Kolte L, Briend A, Friis H, Christensen VB. The immune system in children with malnutrition – a systematic review. PLoS One. (2014) 9:e105017. doi: 10.1371/journal.pone.0105017
3. WHO/UNICEF Ending Preventable Deaths from Pneumonia and Diarrhoea by 2025. New York, NY: UNICEF. (2013).
4. Tate JE, Burton AH, Boschi-Pinto C, Parashar UD, Agocs M, Serhan F, et al. Global, regional, and national estimates of rotavirus mortality in children<5 years of age, 2000-2013. Clin Infect Dis. (2016) 62(Suppl. 2):S96–105. doi: 10.1093/cid/civ1013
5. Lin C-L, Chen S-C, Liu S-Y, Chen K-T. Disease caused by Rotavirus infection.Open Virol J. (2014) 8:14–9. doi: 10.2174/1874357901408010014
6. Kitazawa H, Villena J. Modulation of respiratory TLR3-anti-viral response by probiotic microorganisms: lessons learned from Lactobacillus rhamnosus CRL1505. Front Immunol. (2014) 5:201. doi: 10.3389/fimmu.2014.00201
7. Villena J, Vizoso-Pinto MG, Kitazawa H. Intestinal innate antiviral immunity and immunobiotics: beneficial effects against Rotavirus infection. Front Immunol. (2016) 7:563. doi: 10.3389/fimmu.2016.00563
8. Villena J, Aso H, Rutten VPMG, Takahashi H, van Eden W, Kitazawa H. Immunobiotics for the bovine host: their interaction with intestinal epithelial cells and their effect on antiviral immunity. Front Immunol. (2018) 9:326. doi: 10.3389/fimmu.2018.00326
9. Albarracin L, Kobayashi H, Iida H, Sato N, Nochi T, Aso H, et al. Transcriptomic analysis of the innate antiviral immune response in porcine intestinal epithelial cells: influence of immunobiotic Lactobacilli. Front Immunol. (2017) 8:57. doi: 10.3389/fimmu.2017.00057
10. Villena J, Chiba E, Vizoso-Pinto M, Tomosada Y, Takahashi T, Ishizuka T, et al. Immunobiotic Lactobacillus rhamnosus strains differentially modulate antiviral immune response in porcine intestinal epithelial and antigen presenting cells. BMC Microbiol. (2014) 14:126. doi: 10.1186/1471-2180-14-
11. Tada A, Zelaya H, Clua P, Salva S, Alvarez S, Kitazawa H, et al. Immunobiotic Lactobacillus strains reduce small intestinal injury induced by intraepithelial lymphocytes after Toll-like receptor 3 activation. Inflamm Res. (2016) 65:771–83. doi: 10.1007/s00011-016-0957-7
12. Yamauchi R, Maguin E, Horiuchi H, Hosokawa M, Sasaki Y. The critical role of urease in yogurt fermentation with various combinations of Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus. J Dairy Sci. (2019) 102:1033–43. doi: 10.3168/jds.2018-15192
13. De Keersmaecker SCJ, Braeken K, Verhoeven TLA, Vélez MP, Lebeer S, Vanderleyden J, et al. Flow cytometric testing of green fluorescent protein- tagged lactobacillus rhamnosus GG for response to defensins. Appl Environ Microbiol. (2006) 72:4923–30. doi: 10.1128/AEM.02605-05
14. Biswas EE, Chen PH, Biswas SB. DNA helicase associated with DNA polymerase α: isolation by a modified immunoaffinity chromatography. Biochemistry. (1993) 32:13393–8. doi: 10.1021/bi00212a003
15. Hirose Y, Murosaki S, Fujiki T, Yamamoto Y, Yoshikai Y, Yamashita M. Lipoteichoic acids on Lactobacillus plantarum cell surfaces correlate with induction of interleukin-12p40 production. Microbiol Immunol. (2010) 54:143–51. doi: 10.1111/j.1348-0421.2009.00189.x
16. Moue M, Tohno M, Shimazu T, Kido T, Aso H, Saito T, et al. Toll-like receptor 4 and cytokine expression involved in functional immune response in an originally established porcine intestinal epitheliocyte cell line. Biochim Biophys Acta Gen Subj. (2008) 1780:134–44. doi: 10.1016/j.bbagen.2007.11.006
17. Hosoya S, Villena J, Shimazu T, Tohno M, Fujie H, Chiba E, et al. Immunobiotic lactic acid bacteria beneficially regulate immune response triggered by poly(I:C) in porcine intestinal epithelial cells. Vet Res. (2011) 42:111. doi: 10.1186/1297-9716-42-111
18. Shimazu T, Villena J, Tohno M, Fujie H, Hosoya S, Shimosato T, et al. Immunobiotic Lactobacillus jensenii elicits anti-inflammatory activity in porcine intestinal epithelial cells by modulating negative regulators of the Toll-like receptor signaling pathway. Infect Immun. (2012) 80:276–88. doi: 10.1128/IAI.05729-11
19. Tomosada Y, Villena J, Murata K, Chiba E, Shimazu T, Aso H, et al. Immunoregulatory effect of bifidobacteria strains in porcine intestinal epithelial cells through modulation of ubiquitin-editing enzyme A20 expression. PLoS One. (2013) 8:e59259. doi: 10.1371/journal.pone.0059259
20. Kobayashi H, Albarracin L, Sato N, Kanmani P, Kober AKMH, Ikeda- Ohtsubo W, et al. Modulation of porcine intestinal epitheliocytes immunetranscriptome response by Lactobacillus jensenii TL2937. Benef Microbes. (2016) 7:769–82. doi: 10.3920/BM2016.0095
21. Ishizuka T, Kanmani P, Kobayashi H, Miyazaki A, Soma J, Suda Y, et al. Immunobiotic Bifidobacteria strains modulate Rotavirus immune response in porcine intestinal epitheliocytes via pattern recognition receptor signaling. PLoS One. (2016) 11:e0152416. doi: 10.1371/journal.pone.0152416
22. Bagchi P, Nandi S, Chattopadhyay S, Bhowmick R, Halder UC, Nayak MK, et al. Identification of common human host genes involved in pathogenesis of different rotavirus strains: an attempt to recognize probable antiviral targets. Virus Res. (2012) 169:144–53. doi: 10.1016/j.virusres.2012.07.021
23. Macpherson C, Audy J, Mathieu O, Tompkins TA. Multistrain probiotic modulation of intestinal epithelial cells’ immune response to a double- stranded RNA ligand, poly(i·c). Appl Environ Microbiol. (2014) 80:1692–700. doi: 10.1128/AEM.03411-13
24. Villena J, Chiba E, Tomosada Y, Salva S, Marranzino G, Kitazawa H, et al. Orally administered Lactobacillus rhamnosus modulates the respiratory immune response triggered by the viral pathogen-associated molecular pattern poly(I:C). BMC Immunol. (2012) 13:53. doi: 10.1186/1471-2172-13-53
25. Vélez MP, Verhoeven TLA, Draing C, Von Aulock S, Pfitzenmaier M, Geyer A, et al. Functional analysis of D-alanylation of lipoteichoic acid in the probiotic strain Lactobacillus rhamnosus GG. Appl Environ Microbiol. (2007) 73:3595–604. doi: 10.1128/AEM.02083-06
26. Palumbo E, Deghorain M, Cocconcelli PS, Kleerebezem M, Geyer A, Hartung T, et al. D-alanyl ester depletion of teichoic acids in Lactobacillus plantarum results in a major modification of lipoteichoic acid composition and cell wall perforations at the septum mediated by the Acm2 autolysin. J Bacteriol. (2006) 188:3709–15. doi: 10.1128/JB.188.10.3709-3715.2006
27. Mohamadzadeh M, Pfeiler EA, Brown JB, Zadeh M, Gramarossa M, Managlia E, et al. Regulation of induced colonic inflammation by Lactobacillus acidophilus deficient in lipoteichoic acid. Proc Natl Acad Sci USA. (2011) 108(Suppl. 1):4623–30. doi: 10.1073/pnas.1005066107
28. Bron PA, Tomita S, Mercenier A, Kleerebezem M. Cell surface-associated compounds of probiotic lactobacilli sustain the strain-specificity dogma. Curr Opin Microbiol. (2013) 16:262–9. doi: 10.1016/j.mib.2013.06.001
29. Lee IC, Tomita S, Kleerebezem M, Bron PA. The quest for probiotic effector molecules – unraveling strain specificity at the molecular level. Pharmacol Res. (2013) 69:61–74. doi: 10.1016/j.phrs.2012.09.010
30. Lebeer S, Bron PA, Marco ML, Van Pijkeren JP, O’Connell Motherway M, Hill C, et al. Identification of probiotic effector molecules: present state and future perspectives. Curr Opin Biotechnol. (2018) 49:217–23. doi: 10.1016/j.copbio. 2017.10.007
31. Clua P, Kanmani P, Zelaya H, Tada A, Humayun Kober AKM, Salva S, et al. Peptidoglycan from immunobiotic Lactobacillus rhamnosus improves resistance of infant Mice to respiratory syncytial viral infection and secondary pneumococcal pneumonia. Front Immunol. (2017) 8:948. doi: 10.3389/fimmu. 2017.00948
32. Kanmani P, Albarracin L, Kobayashi H, Hebert EM, Saavedra L, Komatsu R, et al. Genomic characterization of Lactobacillus delbrueckii TUA4408L and evaluation of the antiviral activities of its extracellular Polysaccharides in porcine intestinal epithelial cells. Front Immunol. (2018) 9:2178. doi: 10.3389/ fimmu.2018.02178
33. Grangette C, Nutten S, Palumbo E, Morath S, Hermann C, Dewulf J, et al. Enhanced antiinflammatory capacity of a Lactobacillus plantarum mutant synthesizing modified teichoic acids. Proc Natl Acad Sci USA. (2005) 102:10321–6. doi: 10.1073/pnas.0504084102
34. Claes IJJ, Lebeer S, Shen C, Verhoeven TLA, Dilissen E, De Hertogh G, et al. Impact of lipoteichoic acid modification on the performance of the probiotic Lactobacillus rhamnosus GG in experimental colitis. Clin Exp Immunol. (2010) 162:306–14. doi: 10.1111/j.1365-2249.2010.04228.x
35. Matsuguchi T, Takagi A, Matsuzaki T, Nagaoka M, Ishikawa K, Yokokura T, et al. Lipoteichoic acids from Lactobacillus strains elicit strong tumor necrosis factor alpha-inducing activities in macrophages through toll-like receptor 2. Clin Diagn Lab Immunol. (2003) 10:259–66. doi: 10.1128/CDLI.10.2.259-266.2003
36. Ryu YH, Baik JE, Yang JS, Kang SS, Im J, Yun CH, et al. Differential immunostimulatory effects of Gram-positive bacteria due to their lipoteichoic acids. Int Immunopharmacol. (2009) 9:127–33. doi: 10.1016/j.intimp.2008.10. 014
37. Kim HG, Lee SY, Kim NR, Ko MY, Lee JM, Yi TH, et al. Inhibitory effects of Lactobacillus plantarum lipoteichoic acid. (LTA) on Staphylococcus aureus LTA-induced tumor necrosis factor-alpha production. J Microbiol Biotechnol. (2008) 18:1191–6.
38. Kim HG, Lee SY, Kim NR, Lee HY, Ko MY, Jung BJ, et al. Lactobacillus plantarum lipoteichoic acid down-regulated Shigella flexneri peptidoglycan- induced inflammation. Mol Immunol. (2011) 48:382–91. doi: 10.1016/j. molimm.2010.07.011
39. Kim HG, Kim N-R, Gim MG, Lee JM, Lee SY, Ko MY, et al. Lipoteichoic acid isolated from Lactobacillus plantarum inhibits lipopolysaccharide-induced TNF-α production in THP-1 cells and endotoxin shock in mice. J Immunol. (2008) 180:2553–61. doi: 10.4049/jimmunol.180.4.2553
40. Jeon B, Kim HR, Kim H, Chung DK. In vitro and in vivo downregulation of C3 by lipoteichoic acid isolated from Lactobacillus plantarum K8 suppressed cytokine-mediated complement system activation. FEMS Microbiol Lett. (2016) 363:fnw140. doi: 10.1093/femsle/fnw140
41. Noh SY, Kang SS, Yun CH, Han SH. Lipoteichoic acid from Lactobacillus plantarum inhibits Pam2CSK4-induced IL-8 production in human intestinal epithelial cells. Mol Immunol. (2015) 64:183–9. doi: 10.1016/j.molimm.2014. 11.014
42. Lee B, Yin X, Griffey SM, Marco ML. Attenuation of colitis by Lactobacillus casei BL23 is dependent on the dairy delivery matrix. Appl Environ Microbiol. (2015) 81:6425–35. doi: 10.1128/AEM.01360-15
43. Lebeer S, Claes IJJ, Vanderleyden J. Anti-inflammatory potential of probiotics: Lipoteichoic acid makes a difference. Trends Microbiol. (2012) 20:5–10. doi: 10.1016/j.tim.2011.09.004
44. Kim KW, Kang SS, Woo SJ, Park OJ, Ahn KB, Song KD, et al. Lipoteichoic acid of probiotic Lactobacillus plantarum attenuates poly I: C-induced IL-8 production in porcine intestinal epithelial cells. Front Microbiol. (2017) 8:1827. doi: 10.3389/fmicb.2017.01827
45. Ebert EC. Interleukin 15 is a potent stimulant of intraepithelial lymphocytes.Gastroenterology. (1998) 115:1439–45. doi: 10.1016/S0016-5085(98)70022-8
46. Kinoshita N, Hiroi T, Ohta N, Fukuyama S, Park EJ, Kiyono H. Autocrine IL- 15 mediates intestinal epithelial cell death via the activation of neighboring intraepithelial NK cells. J Immunol. (2002) 169:6187–92. doi: 10.4049/ jimmunol.169.11.6187
47. Trembath AP, Markiewicz MA. More than decoration: roles for natural killer group 2 member D ligand expression by immune cells. Front Immunol. (2018) 9:231. doi: 10.3389/fimmu.2018.00231
48. Zhou R, Wei H, Sun R, Zhang J, Tian Z. NKG2D recognition mediates Toll- like receptor 3 signaling-induced breakdown of epithelial homeostasis in the small intestines of mice. Proc Natl Acad Sci USA. (2007) 104:7512–5. doi: 10.1073/pnas.0700822104
49. Zhou R, Wei H, Sun R, Tian Z. Recognition of double-stranded RNA by TLR3 induces severe small intestinal injury in mice. J Immunol. (2007) 178:4548–56. doi: 10.4049/jimmunol.178.7.4548
50. Hansen CHF, Holm TL, Krych L, Andresen L, Nielsen DS, Rune I, et al. Gut microbiota regulates NKG2D ligand expression on intestinal epithelial cells. Eur J Immunol. (2013) 43:447–57. doi: 10.1002/eji.201242462
51. Serrano AE, Menares-Castillo E, Garrido-Tapia M, Ribeiro CH, Hernández CJ, Mendoza-Naranjo A, et al. Interleukin 10 decreases MICA expression on melanoma cell surface. Immunol Cell Biol. (2011) 89:447–57. doi: 10.1038/icb. 2010.100
52. Kühn R, Löhler J, Rennick D, Rajewsky K, Müller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. (1993) 75:263–74. doi: 10.1016/0092- 8674(93)80068-P
53. Galdeano CM, de Moreno de LeBlanc A, Vinderola G, Bonet ME, Perdigón G. Proposed model: mechanisms of immunomodulation induced by probiotic bacteria. Clin Vaccine Immunol. (2007) 14:485–92. doi: 10.1128/CVI.00406-06
54. Marranzino G, Villena J, Salva S, Alvarez S. Stimulation of macrophages by immunobiotic Lactobacillus strains: influence beyond the intestinal tract. Microbiol Immunol. (2012) 56:771–81. doi: 10.1111/j.1348-0421.2012. 00495.x Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.