scholarly journals Lactobacillus reuteri DSM 17938 Changes the Frequency of Foxp3+ Regulatory T Cells in the Intestine and Mesenteric Lymph Node in Experimental Necrotizing Enterocolitis

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e56547 ◽  
Author(s):  
Yuying Liu ◽  
Nicole Y. Fatheree ◽  
Bridgette M. Dingle ◽  
Dat Q. Tran ◽  
Jon Marc Rhoads
2017 ◽  
Vol 47 (12) ◽  
pp. 2142-2152 ◽  
Author(s):  
Maria Pasztoi ◽  
Joern Pezoldt ◽  
Michael Beckstette ◽  
Christoph Lipps ◽  
Dagmar Wirth ◽  
...  

Blood ◽  
2010 ◽  
Vol 116 (13) ◽  
pp. 2266-2276 ◽  
Author(s):  
Tomohiro Fukaya ◽  
Hideaki Takagi ◽  
Yumiko Sato ◽  
Kaori Sato ◽  
Kawori Eizumi ◽  
...  

Abstract Oral tolerance is a key feature of intestinal immunity, generating systemic tolerance to fed antigens. However, the molecular mechanism mediating oral tolerance remains unclear. In this study, we examined the role of the B7 family members of costimulatory molecules in the establishment of oral tolerance. Deficiencies of B7-H1 and B7-DC abrogated the oral tolerance, accompanied by enhanced antigen-specific CD4+ T-cell response and IgG1 production. Mesenteric lymph node (MLN) dendritic cells (DCs) displayed higher levels of B7-H1 and B7-DC than systemic DCs, whereas they showed similar levels of CD80, CD86, and B7-H2. MLN DCs enhanced the antigen-specific generation of CD4+Foxp3+ inducible regulatory T cells (iTregs) from CD4+Foxp3− T cells rather than CD4+ effector T cells (Teff) relative to systemic DCs, owing to the dominant expression of B7-H1 and B7-DC. Furthermore, the antigen-specific conversion of CD4+Foxp3− T cells into CD4+Foxp3+ iTregs occurred in MLNs greater than in peripheral organs during oral tolerance under steady-state conditions, and such conversion required B7-H1 and B7-DC more than other B7 family members, whereas it was severely impaired under inflammatory conditions. In conclusion, our findings suggest that B7-H1 and B7-DC expressed on MLN DCs are essential for establishing oral tolerance through the de novo generation of antigen-specific CD4+Foxp3+ iTregs.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Fraser L. Collins ◽  
Naiomy Deliz Rios-Arce ◽  
Jonathan D. Schepper ◽  
A. Daniel Jones ◽  
Laura Schaefer ◽  
...  

Abstract Oral treatment with probiotic bacteria has been shown to prevent bone loss in multiple models of osteoporosis. In previous studies we demonstrated that oral administration of Lactobacillus reuteri in healthy male mice increases bone density. The host and bacterial mechanisms of these effects however are not well understood. The objective of this study was to understand the role of lymphocytes in mediating the beneficial effects of L. reuteri on bone health in male mice. We administered L. reuteri in drinking water for 4 weeks to wild type or Rag knockout (lack mature T and B lymphocytes) male mice. While L. reuteri treatment increased bone density in wild type, no significant increases were seen in Rag knockout mice, suggesting that lymphocytes are critical for mediating the beneficial effects of L. reuteri on bone density. To understand the effect of L. reuteri on lymphocytes in the intestinal tissues, we isolated mesenteric lymph node (MLN) from naïve wild type mice. In ex vivo studies using whole mesenteric lymph node (MLN) as well as CD3+ T-cells, we demonstrate that live L. reuteri and its secreted factors have concentration-dependent effects on the expression of cytokines, including anti-inflammatory cytokine IL-10. Fractionation studies identified that the active component of L. reuteri is likely water soluble and small in size (<3 kDa) and its effects on lymphocytes are negatively regulated by a RIP2 inhibitor, suggesting a role for NOD signaling. Finally, we show that T-cells from MLNs treated with L. reuteri supernatants, secrete factors that enhance osterix (transcription factor involved in osteoblast differentiation) expression in MC3T3-E1 osteoblasts. Together, these data suggest that L. reuteri secreted factors regulate T-lymphocytes which play an important role in mediating the beneficial effects of L. reuteri on bone density.


Immunology ◽  
2017 ◽  
Vol 152 (1) ◽  
pp. 52-64 ◽  
Author(s):  
Aya Shiokawa ◽  
Ryutaro Kotaki ◽  
Tomohiro Takano ◽  
Haruyo Nakajima-Adachi ◽  
Satoshi Hachimura

2014 ◽  
Vol 307 (2) ◽  
pp. G177-G186 ◽  
Author(s):  
Yuying Liu ◽  
Dat Q. Tran ◽  
Nicole Y. Fatheree ◽  
J. Marc Rhoads

Necrotizing enterocolitis (NEC) is an inflammatory disease with evidence of increased production of proinflammatory cytokines in the intestinal mucosa. Lactobacillus reuteri DSM 17938 (LR17938) has been shown to have anti-inflammatory activities in an experimental model of NEC. Activated effector lymphocyte recruitment to sites of inflammation requires the sequential engagement of adhesion molecules such as CD44. The phenotype of CD44+CD45RBlo separates T effector/memory (Tem) cells from naive (CD44−CD45RBhi) cells. It is unknown whether these Tem cells participate in the inflammation associated with NEC and can be altered by LR17938. NEC was induced in 8- to 10-day-old C57BL/6J mice by gavage feeding with formula and exposure to hypoxia and cold stress for 4 days. Survival curves and histological scores were analyzed. Lymphocytes isolated from mesenteric lymph nodes and ileum were labeled for CD4, CD44, CD45RB, intracellular Foxp3, and Helios and subsequently analyzed by flow cytometry. LR17938 decreased mortality and the incidence and severity of NEC. The percentage of Tem cells in the ileum and mesenteric lymph nodes was increased in NEC but decreased by LR17938. Conversely, the percentage of CD4+Foxp3+ regulatory T (Treg) cells in the intestine decreased during NEC and was restored to normal by LR17938. The majority of the Treg cells preserved by LR17938 were Helios+ subsets, possibly of thymic origin. In conclusion, LR17938 may represent a useful treatment to prevent NEC. The mechanism of protection by LR17938 involves modulation of the balance between Tem and Treg cells. These T cell subsets might be potential biomarkers and therapeutic targets during intestinal inflammation.


Shock ◽  
2003 ◽  
Vol 20 (6) ◽  
pp. 517-520 ◽  
Author(s):  
Bharat K. Kotadia ◽  
Thyyar M. Ravindranath ◽  
Mashkoor A. Choudhry ◽  
Farah Haque ◽  
Walid Al-Ghoul ◽  
...  

1980 ◽  
Vol 54 (2) ◽  
pp. 75-82 ◽  
Author(s):  
S. B. Lucas ◽  
O. Hassounah ◽  
R. Muller ◽  
M. J. Doenhoff

ABSTRACTObservations on the course of Hymenolepis nana infection in immunosuppressed mice are presented. Treatment of the host with hydrocortisone acetate caused superinfection of the bowel with worms and the development of normal cysticercoids in the mesenteric lymph node and liver. Natural infection of mice deprived of their T-cells by pre-adult thymectomy and administration of antithymocyte serum resulted in superinfection and widespread metastasis of aberrant cysticercoids that were greatly enlarged and without scolices, causing death after about five months. The significance of these findings and their possible relevance to human infection with H. nana are discussed.


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