Back to Search
Start Over
Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells.
- Source :
-
Mucosal immunology [Mucosal Immunol] 2016 Jan; Vol. 9 (1), pp. 194-205. Date of Electronic Publication: 2015 Jun 24. - Publication Year :
- 2016
-
Abstract
- Elevated inflammatory cytokines (EMCs) at mucosal surfaces have been associated with HIV susceptibility, but the underlying mechanisms remain unclear. We characterized the soluble mucosal proteome associated with elevated cytokine expression in the female reproductive tract. A scoring system was devised based on the elevation (upper quartile) of at least three of seven inflammatory cytokines in cervicovaginal lavage. Using this score, HIV-uninfected Kenyan women were classified as either having EMC (n=28) or not (n=68). Of 455 proteins quantified in proteomic analyses, 53 were associated with EMC (5% false discovery rate threshold). EMCs were associated with proteases, cell motility, and actin cytoskeletal pathways, whereas protease inhibitor, epidermal cell differentiation, and cornified envelope pathways were decreased. Multivariate analysis identified an optimal signature of 16 proteins that distinguished the EMC group with 88% accuracy. Three proteins in this signature were neutrophil-associated proteases that correlated with many cytokines, especially GM-CSF (granulocyte-macrophage colony-stimulating factor), IL-1β (interleukin-1β), MIP-3α (macrophage inflammatory protein-3α), IL-17, and IL-8. Gene set enrichment analyses implicated activated immune cells; we verified experimentally that EMC women had an increased frequency of endocervical CD4(+) T cells. These data reveal strong linkages between mucosal cytokines, barrier function, proteases, and immune cell movement, and propose these as potential mechanisms that increase risk of HIV acquisition.
- Subjects :
- Adult
CD4-Positive T-Lymphocytes cytology
Cell Movement immunology
Chemokine CCL20 genetics
Chemokine CCL20 immunology
Cytokines genetics
Cytoskeletal Proteins genetics
Disease Susceptibility
Female
Gene Expression Profiling
Gene Expression Regulation
Genitalia, Female cytology
Genitalia, Female immunology
Granulocyte-Macrophage Colony-Stimulating Factor genetics
Granulocyte-Macrophage Colony-Stimulating Factor immunology
HIV Infections
Humans
Interleukin-17 genetics
Interleukin-17 immunology
Interleukin-1beta genetics
Interleukin-1beta immunology
Interleukin-8 genetics
Interleukin-8 immunology
Kenya
Mucous Membrane cytology
Multivariate Analysis
Peptide Hydrolases genetics
Proteomics
Sex Workers
CD4-Positive T-Lymphocytes immunology
Cytokines immunology
Cytoskeletal Proteins immunology
Mucous Membrane immunology
Peptide Hydrolases immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1935-3456
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Mucosal immunology
- Publication Type :
- Academic Journal
- Accession number :
- 26104913
- Full Text :
- https://doi.org/10.1038/mi.2015.51