Infection and Pregnancy

General Overview:

 

Mor, G. (2020, May 31). Reproductive Immunology. 

In The Biomedical & Life Sciences Collection, Henry Stewart Talks.

 

 

 

 

Trophoblast Biology

Our previous work has demonstrated the expression of Toll-like receptors on trophoblast cells and ligation of these receptors produce a cytokine/chemokine network in response to either endogenous or exogenous stimuli at the maternal fetal interface. Therefore trophoblast cells serve as sensors for the recognition and response to the environment throughout implantation and gestation, suggesting that the trophoblast itself might act as an innate immune cell by recognizing microbial products. We currently are investigating the tight regulation of TLR function and signaling in trophoblast and how this contributes to their immunological role.

Immune Cell Regulation at the Maternal-Fetal Interface

Maternal/fetal macrophages role in tolerance to bacterial infections and response to persistent viral infections. In recognizing and responding to the uterine microenvironment trophoblast may recruit immune cells, such as macrophages, and regulate their distribution and function. We are currently investigating how trophoblast cells induce differentiation of macrophages into a pregnancy-supporting phenotype and how this phenotype is associated with a tolerant response to bacteria to prevent an inflammatory response.

Infection and Pregnancy

Mechanisms of immune, placental, and decidual responses to pathogens leading to preterm labor. In vivo model of preterm in polymicrobial disease. Dr. Mor's laboratory is actively investigating how viral infection may disrupt the fetal-maternal interaction by modifying the function of TLRs Our studies have shown that a viral infection of the placenta and decidua will lead to a disruption in immune cell distribution and function and consequently preterm labor. To further understand the role of infection in pregnancy we have developed an in vivo model looking at the mechanisms in polymicrobial disease at the maternal/fetal interface and preterm labor.

  • Members

    Current Members

     Gil G. Mor, M.D., Ph.D. 

    John M. Malone Jr. MD, Endowed Chair and Scientific Director of The C.S. Mott Center for Human Growth and Development, Vice Chair for Research-Department of Obstetrics and Gynecology

     

     

     

     

    Jiahui Ding, MD, Ph.D.  - Post-Doctoral Fellow

    Jiahui Ding obtained her M.D. in Hubei University of Traditional Chinese Medicine in 2013, Wuhan, China and her Ph.D afterwards in Huazhong University of Science and Technology in 2018. She joined Dr. Mor’s lab at Yale University in 2017 as a postgraduate associate and continued as a postdoctoral associate after she received her PhD Degree in 2018. Dr. Ding moved to the Mott Center in 2019 together with the lab to finish her post-doctoral training. Her study focuses on viral infection during pregnancy. She determined that Interferon-stimulated gene 20 (ISG20) has a crucial role in controlling Zika viral infection in trophoblast cells. Dr. Ding is continuing to explore the anti-viral effects of ISG20 and its other possible functions during the control of viral infection pregnancy.


    Yuan You, M.Sc. - Lab Manager

    Yuan You had his Bachelor Degree at Pharmacy at Capital Medical University in 2010 and received Master Degree at Cellular and Molecular Biology from University of New Haven in 2016. He then started his postgraduate fellowship in the Department of Obstetrics, Gynecology and Reproductive Sciences at Yale University under the supervision of Dr. Mor. He participated the researches in the Reproductive Immunology, especially the studies related to the early embryo implantation. He focuses on the interactions between the developing embryo and the maternal endometrium and creates an 3D In Vivo model to evaluate trophoblast cells migration and invasion. He also studies on the role of IFN during the human pregnancy, and interest in the molecular mechanisms of IFN pathway in the viral infection. 

    Anthony Maxwell - PhD Student

    Anthony received his bachelor’s degree in molecular biology and biotechnology from the University of Michigan in 2017. Afterwards, he completed his master’s degree in molecular biology from the University of Michigan in 2019. His research focused on understanding the maturation and trafficking of a family of serine proteases called proprotein convertases, which are highly relevant in cancer biology. In 2019, Anthony began his PhD in the Physiology department at Wayne State University. Shortly after, he started on the reproductive science concentration and joined the Mor lab. His studies currently focus on how inflammation from viral infections affects the development of the fetal immune system, which can lead to various outcomes such as asthma, allergies, vaccine sensitivity, or susceptibility to infections.

     Anna Hu - Research Assistant

    Anna received her bachelor’s degree in neuroscience from the University of Michigan in 2018. She then completed her master’s degree in physiology from Wayne State University in 2021. Her research focused on developing a placenta specific mouse model to study the role of the placenta during viral infection.

  • Publications

    1          Kwon, J. Y. et al. Relevance of placental type I interferon beta regulation for pregnancy success. Cell Mol Immunol, doi:10.1038/s41423-018-0050-y (2018).

    2          Kwon, J.-Y. et al. Relevance of placental Type I Interferon beta regulation for the success of pregnancy. JCI under review (2018).

    3          Racicot, K. et al. Cutting Edge: Fetal/Placental Type I IFN Can Affect Maternal Survival and Fetal Viral Load during Viral Infection. J Immunol, doi:10.4049/jimmunol.1601824 (2017).

    4          Mor, G., Aldo, P. & Alvero, A. B. The unique immunological and microbial aspects of pregnancy. Nat Rev Immunol, doi:10.1038/nri.2017.64 (2017).

    5          Cross, S. N. et al. Viral Infection Sensitizes Human Fetal Membranes to Bacterial Lipopolysaccharide by MERTK Inhibition and Inflammasome Activation. J Immunol 199, 2885-2895, doi:10.4049/jimmunol.1700870 (2017).

    6          Racicot, K. et al. Type I Interferon Regulates the Placental Inflammatory Response to Bacteria and is Targeted by Virus: Mechanism of Polymicrobial Infection-Induced Preterm Birth. Am J Reprod Immunol 75, 451-460, doi:10.1111/aji.12501 (2016).

    7          Aldo, P. et al. HSV-2 enhances ZIKV infection of the placenta and induces apoptosis in first-trimester trophoblast cells. Am J Reprod Immunol 76, 348-357, doi:10.1111/aji.12578 (2016).

    8          Aldo, P., Marusov, G., Svancara, D., David, J. & Mor, G. Simple Plex() : A Novel Multi-Analyte, Automated Microfluidic Immunoassay Platform for the Detection of Human and Mouse Cytokines and Chemokines. Am J Reprod Immunol 75, 678-693, doi:10.1111/aji.12512 (2016).

    9          Silasi, M. et al. Viral infections during pregnancy. Am J Reprod Immunol 73, 199-213, doi:10.1111/aji.12355 (2015).

    10        Pan, J. et al. Viral Infection-Induced Differential Expression of LncRNAs Associated with Collagen in Mouse Placentas and Amniotic Sacs. Am J Reprod Immunol 74, 237-257, doi:10.1111/aji.12406 (2015).

    11        Gnainsky, Y. et al. Biopsy-induced inflammatory conditions improve endometrial receptivity: the mechanism of action. Reproduction 149, 75-85, doi:10.1530/rep-14-0395 (2015).

    12        Racicot, K. E. et al. Human chorionic gonadotropin enhances trophoblast-epithelial interaction in an in vitro model of human implantation. Reprod Sci 21, 1274-1280, doi:10.1177/1933719114522553 (2014).

    13        Racicot, K., Kwon, J. Y., Aldo, P., Silasi, M. & Mor, G. Understanding the Complexity of the Immune System during Pregnancy. Am J Reprod Immunol 72, 107-116, doi:10.1111/aji.12289 (2014).

    14        Aldo, P. B. et al. Trophoblast Induces Monocyte Differentiation Into CD14+/CD16+ Macrophages. Am J Reprod Immunol 72, 270-284, doi:10.1111/aji.12288 (2014).

    15        Racicot, K. et al. Viral infection of the pregnant cervix predisposes to ascending bacterial infection. J Immunol 191, 934-941, doi:10.4049/jimmunol.1300661 (2013).

    16        Chefetz, I. et al. TLR2 enhances ovarian cancer stem cell self-renewal and promotes tumor repair and recurrence. Cell Cycle 12, 511-521, doi:10.4161/cc.23406 (2013).

    17        Ramhorst, R. et al. Modulation and recruitment of inducible regulatory T cells by first trimester trophoblast cells. Am J Reprod Immunol 67, 17-27, doi:10.1111/j.1600-0897.2011.01056.x (2012).

    18        Holmberg, J. C. et al. An in vitro model for the study of human implantation. Am J Reprod Immunol 67, 169-178, doi:10.1111/j.1600-0897.2011.01095.x (2012).

    19        Hanlon, D. J. et al. Enhanced stimulation of anti-ovarian cancer CD8(+) T cells by dendritic cells loaded with nanoparticle encapsulated tumor antigen. Am J Reprod Immunol 65, 597-609, doi:10.1111/j.1600-0897.2010.00968.x (2011).

    20        Cardenas, I. et al. Placental viral infection sensitizes to endotoxin-induced pre-term labor: a double hit hypothesis. AJRI 65, 110-117, doi:AJI908 [pii]

    10.1111/j.1600-0897.2010.00908.x (2011).

    21        Straszewski-Chavez, S. L., Abrahams, V. M., Aldo, P. B., Romero, R. & Mor, G. AKT controls human first trimester trophoblast cell sensitivity to FAS-mediated apoptosis by regulating XIAP expression. Biol Reprod 82, 146-152, doi:biolreprod.109.078972 [pii]

    10.1095/biolreprod.109.078972 (2010).

    22        Peng, B., Koga, K., Cardenas, I., Aldo, P. & Mor, G. Phagocytosis of apoptotic trophoblast cells by human endometrial endothelial cells induces proinflammatory cytokine production. AJRI 64, 12-19, doi:AJI815 [pii]

    10.1111/j.1600-0897.2010.00815.x (2010).

    23        Gnainsky, Y. et al. Local injury of the endometrium induces an inflammatory response that promotes successful implantation. Fertility and Sterility 94, 2030-2036, doi:10.1016/j.fertnstert.2010.02.022 (2010).

    24        Cardenas, I. et al. Viral infection of the placenta leads to fetal inflammation and sensitization to bacterial products predisposing to preterm labor. J Immunol 185, 1248-1257, doi:10.4049/jimmunol.1000289 (2010).

    25        Cardenas, I. et al. Viral infection of the placenta leads to fetal inflammation and sensitization to bacterial products predisposing to preterm labor. J. Immunol. 185, 1248-1257, doi:jimmunol.1000289 [pii]

    10.4049/jimmunol.1000289 (2010).

    26        Aldo, P. B., Mulla, M. J., Romero, R., Mor, G. & Abrahams, V. M. Viral ssRNA Induces First Trimester Trophoblast Apoptosis through an Inflammatory Mechanism. AJRI, doi:AJI817 [pii]

    10.1111/j.1600-0897.2010.00817.x (2010).

    27        Straszewski-Chavez, S. L. et al. The isolation and characterization of a novel telomerase immortalized first trimester trophoblast cell line, Swan 71. Placenta 30, 939-948, doi:10.1016/j.placenta.2009.08.007 (2009).

    28        Koga, K. et al. Activation of TLR3 in the trophoblast is associated with preterm delivery. Am J Reprod Immunol 61, 196-212, doi:10.1111/j.1600-0897.2008.00682.x (2009).

    29        Koga, K., Aldo, P. B. & Mor, G. Toll-like receptors and pregnancy: trophoblast as modulators of the immune response. J Obstet Gynaecol Res 35, 191-202, doi:JOG963 [pii]

    10.1111/j.1447-0756.2008.00963.x (2009).

    30        Abrahams, V. M. et al. TLR6 modulates first trimester trophoblast responses to peptidoglycan. J Immunol 180, 6035-6043 (2008).

    31        Fest, S. et al. Trophoblast-macrophage interactions: a regulatory network for the protection of pregnancy. Am J Reprod Immunol 57, 55-66 (2007).

    32        Aldo, P. B. et al. A novel three-dimensional in vitro system to study trophoblast-endothelium cell interactions. Am J Reprod Immunol 58, 98-110 (2007).

    33        Abrahams, V. M. et al. Expression and secretion of antiviral factors by trophoblast cells following stimulation by the TLR-3 agonist, Poly(I : C). Hum Reprod 21, 2432-2439 (2006).

    34        Straszewski-Chavez, S. L., Abrahams, V. M., Aldo, P. B. & Mor, G. Isolation and characterization of a novel telomerase-immortalized human first trimester trophoblast cell line. Placenta 26, A.62. (2005).

    35        Mor, G., Romero, R., Aldo, P. B. & Abrahams, V. M. Is the trophoblast an immune regulator?: the role of toll-like receptors during pregnancy. Crit Rev Immunol 25, 375-388 (2005).

    36        Abrahams, V. M. et al. A role for TLRs in the regulation of immune cell migration by first trimester trophoblast cells. J Immunol 175, 8096-8104 (2005).

    37        Abrahams, V. M. et al. Divergent trophoblast responses to bacterial products mediated by TLRs. J Immunol 173, 4286-4296 (2004).