RESUMO
BACKGROUND: There are 2 new phenotypes of HIV-1-positive individuals who exhibit a spontaneous and sustained control of viral replication at least for 1 year without antiretroviral therapy (elite controllers <50 copies/mL and viremic controllers <2000 copies/mL). Mechanisms related to this spontaneous control of viral replication are poorly understood. METHODS: The study included HIV-1 controllers (patients with at least 1 year of HIV-1 diagnosis, highly active antiretroviral therapy naive, and with viral loads less than 2000 copies/mL) and HIV-1 progressors without antiretroviral therapy (viral load >2500 copies/mL, and CD4 T-cell count >250 cells/µL at the time of sampling). The expression of soluble factors, leukocyte protease inhibitor (SLPI) and human α-defensins-1 (HAD-1), was measured by real-time polymerase chain reaction from neutrophil cultures with or without HIV stimulation; the frequency and phenotype of innate and adaptive immune cells were determined by flow cytometry, and frequency of human leukocyte antigen alleles was determined by polymerase chain reaction sequence-specific oligonucleotide typing. RESULTS: As expected, HIV-1 controllers had higher CD4 T-cell counts and lower viral load when compared with HIV-1 progressor individuals; in addition, they exhibited lower expression of activation markers, higher frequency of myeloid dendritic cell, lower percentage of regulatory T cells and natural killer cells, and higher expression of SLPI. CONCLUSIONS: All together, these findings suggest that the control of the immune activation status and the production of antiviral proteins by innate immune cells could be associated to the mechanisms involved in the control of HIV-1 replication and better preservation of the CD4 T-cell count.
Assuntos
Infecções por HIV/imunologia , Sobreviventes de Longo Prazo ao HIV , HIV-1/imunologia , Imunidade Inata , Leucócitos/imunologia , Inibidor Secretado de Peptidases Leucocitárias/biossíntese , Adulto , Alelos , Células Cultivadas , Colômbia , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Antígenos HLA/análise , Antígenos HLA/genética , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Carga Viral , alfa-Defensinas/biossínteseRESUMO
PURPOSE: To describe the presence of secretory leukocyte protease inhibitor (SLPI), a cationic peptide with antimicrobial and antiprotease activity, in the innate ocular immune reaction in a rat model of Staphylococcus aureus endophthalmitis. METHODS: Seventy-five female Lewis rats were divided into three groups: the endophthalmitis group received an intravitreal injection of 65 colony-forming units of viable S. aureus, the vehicle-injected group received balanced sterile saline solution (BSS), and the control group was not injected. Eyes were enucleated at 24 and 48 hours and processed for immunohistochemical staining and Western blot studies for SLPI. RESULTS: In S. aureus endophthalmitis eyes, there was strong immunostaining for SLPI in the retina and vitreous with associated neutrophilic infiltrates. At 48 hours, corneas also stained for SLPI. Western blots confirmed increased SLPI expression in all infected eyes. By immunohistochemical assays, SLPI was absent in the BSS and control eyes. The causative pathogen was identified in all samples from the endophthalmitis group by traditional culture methods. CONCLUSIONS: To our knowledge, this report is the first to demonstrate the presence of SLPI in the inflamed cornea, vitreous, and retina tissues of rat eyes with S. aureus endophthalmitis, suggesting that SLPI has an active role in the innate immunity of the eye. Release of SLPI by inflammatory cells in the anterior and posterior segments may contribute to the host defense response against infectious endophthalmitis.