Abstract
Suppression of immune activation and increased inflammation are prevalent during viral infection. To investigate the role of inflammation in HIV transmission, we studied the infectious and inflammatory milieu in cervical mucosa from HIV-1- and human papillomavirus (HPV)-coinfected and HPV-monoinfected women. The numbers of cytokine-, chemokine-, and p24-expressing cells were determined using in situ imaging analysis and intracellular staining of p24 antigen. Significantly higher expression of the proinflammatory cytokines, interleukin (IL)-1alpha/beta, was seen in cervical tissue from HIV/HPV-coinfected as compared with HPV-monoinfected tissues, whereas IL-2- and interferon (IFN)-gamma-expressing cells were higher in HPV-monoinfected tissues. IL-10 was low in both groups, whereas IL-4 was significantly higher in HPV-monoinfected and HIV/HPV-coinfected tissues than in HIV/HPV-negative controls. RANTES and macrophage inflammatory protein (MIP)-1beta but not MIP-1alpha were significantly higher in the genital tract of HIV/HPV-coinfected as compared with HPV-monoinfected individuals and controls. HIV/HPV-coinfected tissues had a higher level of human leukocyte antigen D-related (HLA-DR)-expressing dendritic cells (DCs). There was a positive correlation between the number of CD4(+) and CD8(+) T cells as well as CD1a, IL-1alpha, and RANTES expression and p24 antigen-expressing cells in the HIV/HPV-coinfected tissues. These findings suggest the persistence of immune activation and inflammation in the genital tract of women with HPV monoinfection and in HIV-infected women coinfected with HPV.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD1 / analysis
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Antigens, CD1 / metabolism
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Biomarkers / analysis
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Case-Control Studies
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Chemokine CCL3
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Chemokine CCL4
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Chemokine CCL5 / analysis
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Chemokine CCL5 / metabolism
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Cohort Studies
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Cytokines / analysis
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Cytokines / metabolism*
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Dendritic Cells / immunology
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Female
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HIV Core Protein p24 / analysis
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HIV Core Protein p24 / metabolism
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HIV Infections / complications*
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HIV Infections / immunology*
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HIV-1
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HLA-DR Antigens / analysis
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HLA-DR Antigens / metabolism
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Humans
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Image Processing, Computer-Assisted
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Interferon-gamma / analysis
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Interferon-gamma / metabolism
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Interleukin-10 / analysis
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Interleukin-10 / metabolism
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Interleukin-1alpha / analysis
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Interleukin-1alpha / metabolism
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Interleukin-2 / analysis
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Interleukin-2 / metabolism
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Interleukin-4 / analysis
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Interleukin-4 / metabolism
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Lymphocyte Subsets / immunology
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Lymphocyte Subsets / pathology
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Macrophage Inflammatory Proteins / analysis
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Macrophage Inflammatory Proteins / metabolism
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Mucous Membrane / immunology
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Mucous Membrane / pathology
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Papillomaviridae
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Papillomavirus Infections / complications*
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Papillomavirus Infections / immunology*
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Papillomavirus Infections / pathology
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Uterine Cervical Diseases / complications*
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Uterine Cervical Diseases / immunology*
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Uterine Cervical Diseases / pathology
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Uterine Cervical Diseases / surgery
Substances
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Antigens, CD1
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Biomarkers
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CD1a antigen
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Chemokine CCL3
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Chemokine CCL4
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Chemokine CCL5
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Cytokines
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HIV Core Protein p24
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HLA-DR Antigens
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Interleukin-1alpha
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Interleukin-2
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Macrophage Inflammatory Proteins
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Interleukin-10
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Interleukin-4
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Interferon-gamma