Reproductive Immunology Publications

Reproductive Immunology Publications

1. Our studies have addressed the active role of the placenta as an immune modulator and demonstrated that the placenta has the capacity to promote cell death of activated maternal immune cells. Through the expression of Fas Ligand (FasL) trophoblast cells can eliminate T cells that represent a danger for the pregnancy. We demonstrated that this process could be obtained either by direct cell to cell contact or by release of microvesicles containing FasL. We also demonstrated that tumor cells use a similar mechanism, initiating the concept that many of the immune modulatory aspects of the placenta share similarities with tumor cells rather than organ transplants.

a) Mor G, Gutierrez LS, Eliza M, Kahyaogili F, Arici A (1998) Induction of apoptosis mediated by the Fas-Fas ligand system in human placental trophoblast and gestational trophoblastic disease. American Journal of Reproductive Immunology: 40:89-94

b) Garcia-Velascol J, Arici A, Naftolin F, Zreick T, Mor G (1999) Macrophage-derived growth factors regulate Fas Ligand expression in endometrial stromal cells. A role in endometriosis. Molecular Human Reproduction. 5:642-650

c) Hsu CD, Basherram H, Lu LC, Meaddough E, Lee, IS, Harirah H, Mor G. (2001) Elevated serum `Fas in preeclampsia. American Journal of Obstetrics and Gynecology. 97:530-532

d) Abrahams VM, Straszewski, SL, Mor G (2004) First Trimester Trophoblast Cells Secrete Whole Fas Ligand Which Induces Fas-Mediated Apoptosis In Immune Cells. Molecular Human Reproduction. 10 (1): 55-63

2. Our studies have elucidated the role of immune cells during pregnancy. We characterized the interaction between the trophoblast and immune cells and their specific function required for the success of pregnancy. We demonstrated that contrary to initial thought, maternal immune cells are required for the success of the pregnancy and their phenotype is determined by factors secreted by the trophoblast. We introduced the biological evidence in support of the concept of the placenta as an immune regulator.

a) Abrahams, VM, Kim YM, Straszewski S, Romero R, Mor G (2004) Macrophages and apoptotic cell clearance during pregnancy. American Journal of Reproductive Immunology: 51:275-282

b) Plaks V, Birnberg, T, Berkutzki, T, Kalchenko, V, Mor G, Dekel N, Neeman M, and Jung S (2008) Uterine Dendritic cells are crucial for Decidua Formation during Embryo Implantation. Journal of Clinical Investigation. 118 (2): 3954-65

c) Ramhorst R, Fraccaroli L, Aldo P, Alvero AB, Cardenas I, Leiros CP, Mor G (2011) Modulation and Recruitment of Inducible Regulatory T Cells by First Trimester Trophoblast Cells. American Journal of Reproductive Immunology. Aug 7, PMID: 21819477

d) Aldo PB, Racicot K, Craviero V, Guller S, Romero R, Mor G (2014) Trophoblast Induces Monocyte Differentiation Into CD14+/CD16+ Macrophages. American Journal of Reproductive Immunology. 2014 Sep;72(3):270-84. Doi: 10.1111/aji.12288. Epub 2014 Jul 3. PMID: 24995492

3. In order to understand how the placenta might regulate the maternal immune cells, we need to elucidate the mechanism by which trophoblast cells are able to recognize the microenvironment and respond to factors present at the implantation site. We have made significant contributions to understanding the role of Toll Like Receptors at the maternal fetal interface and its responses to microbial products.

a) Abrahams VM, Aldo P, Kim YM, Straszewski-Chavez S, Chaiworapongsa T, Romero R, Mor G. (2004) Divergent Trophoblast Responses To Bacterial Products Mediated By Toll-Like Receptors. Journal of Immunology: 173:4286-4296

b) Abrahams VM, Schaefer TM, Fahey JV, Visintin I, Wright JA, Aldo PB, Romero R, Wira CR, Mor G (2006) Expression and secretion of antiviral factors by trophoblast cells following stimulation by the TLR-3 agonist, Poly(I : C). (2006) Human Reproduction. 3 21(9):2432-9.

c) Kim YM, Romero R Chaiworapongsa T, Kim GJ, Kim MR, Kuivaniemi SH, Tromp G, Abrahams VM and Mor G. (2004) Protein and mRNA expression for the pattern recognition receptors Toll-like receptor-2 and –4 are increased in spontaneous labor at term and histologic chorioamnionitis. American Journal of Obstetrics and Gynecology; 191(4):1346-55

d) Koga K, Cardenas I, Aldo, P, Abrahams, V, Peng, B, Fill S, Romero, R, Mor G (2009) Activation of TLR3 in the trophoblast is associated with preterm labor. American Journal of Reproductive Immunology: 61(3):196-212

4. We have focused on understanding the role of microbial and microbial products in the modulation of trophoblast immune responses. We were the first ones to propose that pregnancy complications, such as preterm birth may be the result of polymicrobial infections. We have elucidated some of the cellular pathways associated with viral infection and its repercussion in the normal response to bacterial products. Our research has demonstrated that viral infections might be a major factor disrupting the normal hemostasis established by the placenta and maternal immune system. Furthermore, we have investigated the mechanism mediating the response to infection and the consequence of inflammation in pregnancy and the fetus.

a) Cardenas I, Mor G, Aldo P, Lang SM, Stabach P, Sharp A, Romero R, Mazaki-Tovi, S, Gervasi MT, Means RE, (2010) Placental Viral Infection Sensitizes to LPS-Induced Pre-Term Labor: The Double Hit Hypothesis, American Journal of Reproductive Immunology.

b) Cardenas I, Means RE, Aldo PB, Koga K, Lang SM, Booth C, Manzur A, Oyarzun E, Romero R, Mor G, (2010) Viral infection of the placenta leads to fetal inflammation and sensitization to bacterial products predisposing to preterm labor. Journal of Immunology;185(2):1248-57. PMID: 20554966

c) Racicot K, Cardenas I, Wünsche V, Aldo P, Guller S, Means RE, Romero R, Mor G (2013) Viral infection of the pregnant cervix predisposes to ascending bacterial infection. Journal of Immunology. 2013 Jul 15;191(2):934-41. PMID: 23752614

d) Gervasi MT, Romero R, Bracalente G, Chaiworapongsa T, Erez O, Dong Z, Hassan SS, Yeo L, Yoon BH, Mor G, Barzon L, Franchin E, Militello V, Palù G. (2012) Viral invasion of the amniotic cavity (VIAC) in the midtrimester of pregnancy. J Matern Fetal Neonatal Med. 2012 Apr 23. PMID: 22524157

Complete List of Publications in :

http://www.ncbi.nlm.nih.gov/myncbi/collections/bibliography/47921629/