Placenta specific immune regulation and relationship with placental malaria infection

Lead Research Organisation: MRC Unit, The Gambia

Abstract

Malaria parasites can get stuck in the placenta in pregnant women leading to an increased likelihood of death and illness in the mother and child. There are a group of cells present in the body called regulatory T cells (Treg) that can dampen down immune responses and inflammation when an infection occurs. The role of these cells in infection and inflammation is poorly understood. The overall aim of this study is to understand the role that Treg cells play in the immune response to placental malaria infection. In this study we will use special techniques to look for Treg cells in woman with and without malaria infection of the placenta. This will allow us to establish whether Tregs accumulate in the placenta during malaria infection compared to uninfected placentas. This is important since it will help us to understand how the immune response is regulated during placental malaria infection. It is also important because it is difficult to get tissue samples from humans and hence most immune studies in humans are carried out using blood samples. This study will tell us whether what we observe in the placental tissue mirrors the results from blood samples. If we can understand exactly what placental malaria infection does to the mothers and babies this may offer new ways to treat them and prevent the complications.

Technical Summary

We are investigating the immunoregulatory effects of placental malaria infection at birth. The aim of this study is to examine malaria infected and uninfected placental biopsy samples for the regulatory factors Foxp3, IL-10 and TGF-beta using immunohistochemical staining. These results will then be compared with cord blood and maternal peripheral blood results to analyse whether there is any correlation between local regulation in the placenta and in mother and newborn peripheral blood. This is a retrospective cohort study using stored placental biopsy samples taken from women and preserved in formalin at birth. We also propose to analyse whether the same factors can be amplified from RNA extracted from the placental tissue using samples that are collected and stored prospectively. The results should provide valuable information about tissue specific immune regulation, and whether recruitment of regulatory T cells to a site of infection is reflected in peripheral blood samples (cord and maternal). This is of particular importance since there is very little information about tissue specific immune regulation in humans due to difficulties in obtaining tissue from healthy subjects. It will also indicate whether the peripheral blood measurements that are commonly made in human studies have any correlation with what goes on at the tissue site of infection.
 
Description Government Feedback Meetings 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Regular meetings have been held with the Gambia Government Department of State for Health (DoSH) Expanded Programme on Immunization (EPI) Team and National TB Programme to discuss ongoing research and to provide feedback about ongoing studies.

Improved relations with Gambia Government DoSH.
Year(s) Of Engagement Activity 2007,2008
 
Description Sukuta Health Centre Open Day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact This public meeting intended to feed back the results of infant immunology studies to the partcipating familes was also attended by local and central government, community dignatories, religious leaders and school children. Approximately 500 people attended the oral presentations in the morning, and many stayed for the poster session in the afternoon at which our research activities were described.

This led to increased recruitment and retention in our infant immunology studies and greater community support for our work.
Year(s) Of Engagement Activity 2007
 
Description Sukuta Health Centre Open Days 2007 / 2008 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Participants in your research and patient groups
Results and Impact One day event held at the MRC field site where the study subjects are recruited. All parents and study children, local public figures and members of the government were invited to attend and get feedback about the study in the form of oral and poster presentations.

The open day was featured on local television and radio. The recruitment rates in our studies increased after the event.
Year(s) Of Engagement Activity 2007,2008