title: A systems biology examination of the human female genital tract shows compartmentalization of immune factor expression.
abstract: Many mucosal factors in the female genital tract (FGT) have been associated with HIV susceptibility, but little is known about their anatomical distribution in the FGT compartments. This study comprehensively characterized global immune factor expression in different tissue sites of the lower and upper FGT by using a systems biology approach. Tissue sections from the ectocervix, endocervix, and endometrium from seven women who underwent hysterectomy were analyzed by a combination of quantitative mass spectrometry and immunohistochemical staining. Of the >1,000 proteins identified, 281 were found to be differentially abundant in different tissue sites. Hierarchical clustering identified four major functional pathways distinguishing compartments, including innate immune pathways (acute-phase response, LXR/RXR) and development (RhoA signaling, gluconeogenesis), which were enriched in the ectocervix/endocervix and endometrium, respectively. Immune factors important for HIV susceptibility, including antiproteases, immunoglobulins, complement components, and antimicrobial factors, were most abundant in the ectocervix/endocervix, while the endometrium had a greater abundance of certain factors that promote HIV replication. Immune factor abundance is heterogeneous throughout the FGT and shows unique immune microenvironments for HIV based on the exposure site. This may have important implications for early events in HIV transmission and site-specific susceptibility to HIV in the FGT.
authors: University of Manitoba, Department of Medical Microbiology, Winnipeg, Manitoba, Canada. burgener@cc.umanitoba.ca
authors: Adam
authors: A
authors: Burgener
authors: Annelie
authors: A
authors: Tjernlund
authors: Tove
authors: T
authors: Kaldensjo
authors: Max
authors: M
authors: Abou
authors: Stuart
authors: S
authors: McCorrister
authors: Garrett R
authors: GR
authors: Westmacott
authors: Kenzie
authors: K
authors: Mogk
authors: Emma
authors: E
authors: Ambrose
authors: Kristina
authors: K
authors: Broliden
authors: Blake
authors: B
authors: Ball
mesh_terms: D000328:Adult; D005260:Female; D005836:Genitalia, Female / Q000276:immunology* / Q000821:virology; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D011506:Proteins / Q000235:genetics* / Q000276:immunology; D059467:Transcriptome
chemical_list: D011506:Proteins