RATIONALE: Chorioamnionitis induces preterm delivery and acute involution of the fetal thymus which is associated with postnatal inflammatory disorders. We studied the immune response, cell composition, and architecture of the fetal thymus following intraamniotic lipopolysaccharide (LPS) exposure. METHODS: Time-mated ewes received an intraamniotic injection of LPS 5, 12, or 24 hours or 2, 4, 8, or 15 days before delivery at 125 days gestational age (term = 150 days). RESULTS: The LPS exposure resulted in decreased blood lymphocytes within 5 hours and decreased thymic corticomedullary ratio within 24 hours. Thymic interleukin 6 (IL6) and IL17 messenger RNA (mRNA) increased 5-fold 24 hours post-LPS exposure. Increased toll-like receptor 4 (TLR4) mRNA and nuclear factor κB positive cells at 24 hours after LPS delivery demonstrated acute thymic activation. Both TLR4 and IL1 mRNA increased by 5-fold and the number of Foxp3-positive cells (Foxp3+ cells) decreased 15 days after exposure. CONCLUSION: Intraamniotic LPS exposure caused a proinflammatory response, involution, and a persistent depletion of thymic Foxp3+ cells indicating disturbance of the fetal immune homeostasis.
RATIONALE: Chorioamnionitis induces preterm delivery and acute involution of the fetal thymus which is associated with postnatal inflammatory disorders. We studied the immune response, cell composition, and architecture of the fetal thymus following intraamniotic lipopolysaccharide (LPS) exposure. METHODS: Time-mated ewes received an intraamniotic injection of LPS 5, 12, or 24 hours or 2, 4, 8, or 15 days before delivery at 125 days gestational age (term = 150 days). RESULTS: The LPS exposure resulted in decreased blood lymphocytes within 5 hours and decreased thymic corticomedullary ratio within 24 hours. Thymic interleukin 6 (IL6) and IL17 messenger RNA (mRNA) increased 5-fold 24 hours post-LPS exposure. Increased toll-like receptor 4 (TLR4) mRNA and nuclear factor κB positive cells at 24 hours after LPS delivery demonstrated acute thymic activation. Both TLR4 and IL1 mRNA increased by 5-fold and the number of Foxp3-positive cells (Foxp3+ cells) decreased 15 days after exposure. CONCLUSION: Intraamniotic LPS exposure caused a proinflammatory response, involution, and a persistent depletion of thymic Foxp3+ cells indicating disturbance of the fetal immune homeostasis.
Authors: Claudio De Felice; Giuseppe Latini; Antonio Del Vecchio; Paolo Toti; Franco Bagnoli; Felice Petraglia Journal: Pediatrics Date: 2002-08 Impact factor: 7.124
Authors: Estelle Bettelli; Yijun Carrier; Wenda Gao; Thomas Korn; Terry B Strom; Mohamed Oukka; Howard L Weiner; Vijay K Kuchroo Journal: Nature Date: 2006-04-30 Impact factor: 49.962
Authors: Jacqueline M Melville; Robert J Bischof; Els N Meeusen; Alana J Westover; Timothy J M Moss Journal: Reprod Sci Date: 2012-03-14 Impact factor: 3.060
Authors: J Pagel; A Hartz; J Figge; C Gille; S Eschweiler; K Petersen; L Schreiter; J Hammer; C M Karsten; D Friedrich; E Herting; W Göpel; J Rupp; C Härtel Journal: Clin Exp Immunol Date: 2016-06-12 Impact factor: 4.330
Authors: Suhas G Kallapur; Pietro Presicce; Cesar M Rueda; Alan H Jobe; Claire A Chougnet Journal: Semin Reprod Med Date: 2014-01-03 Impact factor: 1.303
Authors: Cesar M Rueda; Casey B Wells; Tate Gisslen; Alan H Jobe; Suhas G Kallapur; Claire A Chougnet Journal: Hum Immunol Date: 2014-11-08 Impact factor: 2.850
Authors: Suhas G Kallapur; Pietro Presicce; Paranthaman Senthamaraikannan; Manuel Alvarez; Alice F Tarantal; Lisa M Miller; Alan H Jobe; Claire A Chougnet Journal: J Immunol Date: 2013-06-21 Impact factor: 5.422
Authors: Jodi K Regan; Paranthaman S Kannan; Matthew W Kemp; Boris W Kramer; John P Newnham; Alan H Jobe; Suhas G Kallapur Journal: Reprod Sci Date: 2015-07-07 Impact factor: 3.060
Authors: Cesar M Rueda; Pietro Presicce; Courtney M Jackson; Lisa A Miller; Suhas G Kallapur; Alan H Jobe; Claire A Chougnet Journal: J Immunol Date: 2016-04-01 Impact factor: 5.422
Authors: Cathelijne Heymans; Marcel den Dulk; Kaatje Lenaerts; Lara R Heij; Ilse H de Lange; Mhamed Hadfoune; Chantal van Heugten; Boris W Kramer; Alan H Jobe; Masatoshi Saito; Matthew W Kemp; Tim G A M Wolfs; Wim G van Gemert Journal: Sci Rep Date: 2021-05-14 Impact factor: 4.379
Authors: Robert Para; Roberto Romero; Derek Miller; Jose Galaz; Bogdan Done; Azam Peyvandipour; Meyer Gershater; Li Tao; Kenichiro Motomura; Douglas M Ruden; Jenna Isherwood; Eunjung Jung; Tomi Kanninen; Roger Pique-Regi; Adi L Tarca; Nardhy Gomez-Lopez Journal: Immunohorizons Date: 2021-09-14
Authors: Augusto F Schmidt; Paranthaman S Kannan; Matthew W Kemp; Boris W Kramer; John P Newnham; Alan H Jobe; Suhas G Kallapur Journal: Pediatr Res Date: 2014-08-08 Impact factor: 3.756