RESUMO
OBJECTIVES: Dendritic cells (DCs) are among the first cells to encounter HIV after mucosal exposure and can bind virus via C-type lectin receptors (CLRs). Here, we characterized the distribution of various DC subtypes and the density of the CLRs, DC-SIGN, langerin, and mannose receptor in the ectocervix of HIV-seronegative women with low- and high-risk behavior for acquiring HIV. MATERIAL AND METHODS: Cryosections from ectocervical biopsies, collected from sexually active low-risk healthy HIV immunoglobulin G-negative women (n = 10) and HIV immunoglobulin G-negative commercial sex workers (n = 8), were assessed by computerized image analysis. RESULTS: We identified various distinct DC populations. CD11c(-)CD1a(+)langerin(+) cells were localized in the epithelium, whereas CD11c(+)CD1a(-)DC-SIGN and CD11c(-)CD1a(-)CD68(+)DC-SIGN(+)mannose receptor(+) cells were restricted to the lamina propria of the ectocervix. CD123(+) cells were found at low incidence and did not express any of the investigated CLRs. The density of CLR expression was significantly higher in the high-risk as compared with the low-risk women. CONCLUSIONS: The superficial and abundant presence of potential HIV target cells makes the ectocervix a likely site for HIV transmission. The detected variations in density and localization of potential HIV receptors should be considered when developing topical prophylactic measures.
Assuntos
Antígenos CD/metabolismo , Moléculas de Adesão Celular/metabolismo , Colo do Útero/metabolismo , Células Dendríticas/imunologia , Infecções por HIV/transmissão , Lectinas Tipo C/metabolismo , Lectinas de Ligação a Manose/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores Mitogênicos/metabolismo , Adulto , Antígenos CD/imunologia , Moléculas de Adesão Celular/imunologia , Colo do Útero/imunologia , Colo do Útero/virologia , Células Dendríticas/virologia , Feminino , Infecções por HIV/imunologia , Humanos , Lectinas Tipo C/imunologia , Lectinas de Ligação a Manose/imunologia , Pessoa de Meia-Idade , Receptores de Superfície Celular/imunologia , Receptores Mitogênicos/imunologiaRESUMO
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.
Assuntos
Citocinas/metabolismo , Infecções por HIV/complicações , Infecções por HIV/imunologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/imunologia , Doenças do Colo do Útero/complicações , Doenças do Colo do Útero/imunologia , Antígenos CD1/análise , Antígenos CD1/metabolismo , Biomarcadores/análise , Estudos de Casos e Controles , Quimiocina CCL3 , Quimiocina CCL4 , Quimiocina CCL5/análise , Quimiocina CCL5/metabolismo , Estudos de Coortes , Citocinas/análise , Células Dendríticas/imunologia , Feminino , Proteína do Núcleo p24 do HIV/análise , Proteína do Núcleo p24 do HIV/metabolismo , HIV-1 , Antígenos HLA-DR/análise , Antígenos HLA-DR/metabolismo , Humanos , Processamento de Imagem Assistida por Computador , Interferon gama/análise , Interferon gama/metabolismo , Interleucina-10/análise , Interleucina-10/metabolismo , Interleucina-1alfa/análise , Interleucina-1alfa/metabolismo , Interleucina-2/análise , Interleucina-2/metabolismo , Interleucina-4/análise , Interleucina-4/metabolismo , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/patologia , Proteínas Inflamatórias de Macrófagos/análise , Proteínas Inflamatórias de Macrófagos/metabolismo , Mucosa/imunologia , Mucosa/patologia , Papillomaviridae , Infecções por Papillomavirus/patologia , Doenças do Colo do Útero/patologia , Doenças do Colo do Útero/cirurgiaRESUMO
OBJECTIVE: Intraarticular corticosteroids are frequently used as successful adjuvant therapy for inflammatory arthritides, but little is known about their effects on molecules that regulate bone biology. We undertook this study to investigate the effect of intraarticular corticosteroids on the synovial expression of RANKL and osteoprotegerin (OPG). METHODS: We evaluated RANKL, OPG, and surface marker expression by immunohistochemical methods in synovial knee biopsy samples obtained from 13 patients with inflammatory arthritis before and 2 weeks following intraarticular injection of triamcinolone hexacetonide. We further investigated the effect of dexamethasone (DEX) on RANKL expression by lymphocytes from rheumatoid arthritis synovial fluids (RA SF), using flow cytometric analysis. Finally, we evaluated the in vitro effect of DEX on RANKL and OPG expression in osteoblast-like cells, by Western blotting. RESULTS: Intraarticular corticosteroids induced a decrease in the number of synovial T cells without influencing the number of macrophages, evaluated as both CD68+ and CD163+ cells. This change was paralleled by a decrease of synovial RANKL expression with a concomitant reduction of the RANKL:OPG ratio. DEX down-regulated RANKL expression on lymphocytes derived from RA SF. Moreover, in vitro pretreatment of osteoblast-like cells with tumor necrosis factor favored an antiresorptive effect of DEX treatment through a similar down-regulation of RANKL expression. CONCLUSION: The decrease in inflammation attributed to intraarticular corticosteroids is accompanied by down-modulation of bone destruction markers. These findings offer a rationale for the beneficial effect of corticosteroids on joint erosion in arthritis.