Abstract
Studies of the immunological environment in the female genital tract (FGT) are critical for the development of vaccines or microbicides to halt the spread of sexually transmitted infections. Challenges arise due to the difficulties of sampling from this site, and the majority of studies have been conducted utilising peripheral blood mononuclear cells. Identifying functional differences between immune cells of the FGT and peripheral blood would aid in our understanding of mucosal immunology. We compared the gene expression profile of mononuclear cells at these two sites. Messenger RNA expression analysis was performed using gene expression arrays on matched cervical mononuclear cells and peripheral blood mononuclear cells. Further cellular phenotyping was done by 10 colour flow cytometry. Of the 22,185 genes expressed by these samples, 5345 genes were significantly differentially expressed between the cell populations. Most differences can be explained by significantly lower levels of T and B cells and higher levels of macrophages and dendritic cells in the FGT compared with peripheral blood. Several immunologically relevant pathways such as apoptosis and innate immune signalling, and a variety of cytokines and cytokine receptors were differentially expressed. This study highlights the importance of the unique immunological environment of the FGT and identifies important differences between systemic and mucosal immune compartments.
Highlights
A major global public health issue is the large number of sexually transmitted infections (STIs), at least four of which, Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Human Papilloma Virus (HPV) and Herpes simplex virus type 2 (HSV-2), remain incurable
In Sub-Saharan Africa, one of the regions hardest hit by the HIV/AIDS epidemic, the primary route of HIV-1 infection is through vaginal intercourse and a disproportionately higher number of women become infected than men [3,4]
Of the 24,500 genes represented on the Illumina HumanRef8 gene expression BeadChip array, 47% of genes (11,586) were expressed in at least one cervical mononuclear cell (CMC) or peripheral blood mononuclear cell (PBMC) sample
Summary
A major global public health issue is the large number of sexually transmitted infections (STIs), at least four of which, Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Human Papilloma Virus (HPV) and Herpes simplex virus type 2 (HSV-2), remain incurable. Vaccines are available for both HBV [1] and HPV [2]; no vaccine is available for HIV, (with an estimated 33.2 million infections), or HSV-2 (with an estimated global prevalence of 37%). There has been increased research into microbicides; the failure of several microbicide trials for HIV-1, including those for nonoxynol-9 and cellulose sulphate, demonstrates a fundamental lack of knowledge of the immunobiology of the female genital tract (FGT) [6,7,8]. A more thorough understanding of the FGT would greatly benefit research efforts concerning all STIs, but HIV-1
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