title: Probiotic bacteria prevent Salmonella - induced suppression of lymphoproliferation in mice by an immunomodulatory mechanism.
abstract: Salmonella enterica infections often exhibit a form of immune evasion. We previously observed that probiotic bacteria could prevent inhibition of lymphoproliferation and apoptosis responses of T cells associated with S. enterica infections in orally challenged mice.
  
  
  
  In this study, changes in expression of genes related to lymphocyte activation in mucosa-associated lymphoid tissues (MALT) of mice orally infected with S. enterica with and without treatment with probiotic bacteria were evaluated. Probiotic bacteria increased expression of mRNA for clusters of differentiation antigen 2 (Cd2), protein tyrosine phosphatase receptor type C (Ptprc), and Toll-like receptor 6 (Tlr6) genes related to T and B cell activation in mouse intestinal tissue. The probiotic bacteria were also associated with reduced mRNA expression of a group of genes (RelB, Myd88, Iκκa, Jun, Irak2) related to nuclear factor of kappa light chains enhancer in B cells (NF-κB) signal transduction pathway-regulated cytokine responses. Probiotic bacteria were also associated with reduced mRNA expression of apoptotic genes (Casp2, Casp12, Dad1, Akt1, Bad) that suggest high avidity lymphocyte sparing. Reduced CD2 immunostaining in mesenteric lymph nodes (MLN) was suggestive of reduced lymphocyte activation in probiotic-treated mice. Reduced immunostaining of TLR6 in MALT of probiotic-treated, S. enterica-infected mice suggests that diminished innate immune sensitivity to S. enterica antigens is associated with preventing lymphocyte deletion.
  
  
  
  The results of this study are consistent with prevention of S. enterica-induced deletion of lymphocytes by the influence of probiotic bacteria in mucosal lymphoid tissues of mice.
authors.affiliation: Microbiology Division, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR, 72079, USA. doug.wagner@fda.hhs.gov.
authors.forename: R Doug
authors.initials: RD
authors.lastname: Wagner
authors.affiliation: Microbiology Division, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR, 72079, USA.
authors.forename: Shemedia J
authors.initials: SJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism; D018801:CD2 Antigens / Q000096:biosynthesis / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects*; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D056747:Immunomodulation; D007165:Immunosuppression Therapy; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000235:genetics; D008198:Lymph Nodes; D008214:Lymphocytes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010581:Peyer's Patches / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D019936:Probiotics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012481:Salmonella Infections, Animal / Q000517:prevention & control*; D019779:Salmonella enterica / Q000472:pathogenicity*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013154:Spleen; D013601:T-Lymphocytes / Q000187:drug effects*; D051216:Toll-Like Receptor 6 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018801:CD2 Antigens; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; C495369:Tlr6 protein, mouse; D051216:Toll-Like Receptor 6; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse
keywords: Apoptosis; Gene expression; Probiotic; Salmonella; Signal transduction genes