ABSTRACT
Air pollution is a serious environmental issue worldwide in developing countries' megacities, affecting the population's health, including the ocular surface, by predisposing or exacerbating other ocular diseases. Herpes simplex keratitis (HSK) is caused by the herpes simplex virus type 1 (HSV-1). The primary or recurring infection in the ocular site causes progressive corneal scarring that may result in visual impairment. The present study was designed to study the immunopathological changes of acute HSK under urban polluted air, using the acute HSK model combined with an experimental urban polluted air exposure from Buenos Aires City. We evaluated the corneal clinical outcomes, viral DNA and pro-inflammatory cytokines by RT-PCR and ELISA assays, respectively. Then, we determined the innate and adaptive immune responses in both cornea and local lymph nodes after HSV-1 corneal by immunofluorescence staining and flow cytometry. Our results showed that mice exposed to polluted air develop a severe form of HSK with increased corneal opacity, neovascularization, HSV-1 DNA and production of TNF-α, IL-1ß, IFN-γ, and CCL2. A high number of corneal resident immune cells, including activated dendritic cells, was observed in mice exposed to polluted air; with a further significant influx of bone marrow-derived cells including GR1+ cells (neutrophils and inflammatory monocytes), CD11c+ cells (dendritic cells), and CD3+ (T cells) during acute corneal HSK. Moreover, mice exposed to polluted air showed a predominant Th1 type T cell response over Tregs in local lymph nodes during acute HSK with decreased corneal Tregs. These findings provide strong evidence that urban polluted air might trigger a local imbalance of innate and adaptive immune responses that exacerbate HSK severity. Taking this study into account, urban air pollution should be considered a key factor in developing ocular inflammatory diseases.
Subject(s)
Air Pollution/adverse effects , Environmental Exposure/adverse effects , Keratitis, Herpetic/etiology , Keratitis, Herpetic/pathology , Animals , Biomarkers , Cornea/immunology , Cornea/metabolism , Cornea/pathology , Corneal Opacity/diagnostic imaging , Corneal Opacity/etiology , Corneal Opacity/metabolism , Corneal Opacity/pathology , Cytokines/metabolism , Disease Models, Animal , Disease Progression , Disease Susceptibility , Fluorescent Antibody Technique , Herpesvirus 1, Human , Humans , Immunophenotyping , Keratitis, Herpetic/diagnostic imaging , Keratitis, Herpetic/metabolism , Mice , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolismABSTRACT
Objective To establish an epidemiological surveillance of viral herpes encephalitis in major hospitals of Monteria, Cordoba. Methods From September 2009 to December 2011, a descriptive study of cases of viral encephalitis was made in three hospitals in the city of Monteria. Cerebrospinal fluid (CSF) samples from 118 patients were included in the study. Clinical aspects, as well as cytochemical and microbiological analysis (Gram stain and culture) of CSF, were used for selecting the patients. Virus detection was performed by using multiplex nested PCR for Herpes simplex virus 1 and 2, Epstein Barr virus, Cytomegalovirus and Varicella zoster virus. Results Viral DNA of herpesvirus was detected in the CSFs of 30 (25.4 %) participants, as follows: 22 (18.6 %) Herpes simplex 1 and 2 viruses, 4 (3.3 %) Cytomegalovirus and 1 (0.8 %) Varicella zoster virus. Co-infections were observed in 3 patients (2.5 %), 1 case by HSV-VZV and 2 cases by CMV/HSV. The clinical manifestations of the patients included: headache (18.6 %), fever (14.4 %), asthenia (10.1 %), seizures (9.3 %), vomiting (8.4 %), and stiff neck (5.9 %). Thirty percent of the patients also had HIV-AIDS. A case fatality rate of 20 % was observed for the patients. Conclusions This paper shows that herpesvirus is a cause of infection of the CNS in patients from Cordoba. This study contributes to the epidemiology of encephalitis, as well as to patient management.(AU)
Objetivo Establecer una vigilancia epidemiológica de la encefalitis viral herpética en los principales hospitales de Montería, Córdoba. Materiales y Métodos Se realizó un estudio descriptivo de los casos de encefalitis viral entre septiembre de 2009 diciembre de 2011 en tres hospitales en la ciudad de Montería. Las muestras líquido cefalorraquídeo (LCR) de 118 pacientes fueron incluidos en el estudio. Los aspectos clínicos como el análisis citoquímico y microbiológico (tinción de Gram y cultivo) de LCR fueron utilizados para la selección de los pacientes. La detección de virus se realizó por PCR anidada multiplex para Herpes simplex virus 1 y 2, virus de Epstein Barr, virus zoster de la varicela y el citomegalovirus. Resultados Se detectó ADN viral del virus del herpes en 30 (25,4 %) muestras de LCR en los pacientes de la siguiente manera: 22 (18,6 %) Herpes simplex virus 1 y 2, 4 (3,3 %) Citomegalovirus y 1 (0,8 %) del virus de la varicela zóster. Se observaron Co-infecciones en 3 pacientes (2,5 %), 1 caso por el VHS-VZV y 2 casos por CMV / HSV. Las manifestaciones clínicas de los pacientes fueron: cefalea (18,6 %), fiebre (14,4 %), astenia (10,1 %), convulsiones (9,3 %), vómitos (8,4 %), y rigidez de nuca (5,9 %). El treinta por ciento de los pacientes también tenía VIH-SIDA. Se observó una tasa de letalidad del 20 % de los pacientes. Conclusiones Se demuestra que el herpesvirus es causa de infección del SNC en pacientes en Córdoba. Este estudio contribuye a la caracterización serológica viral epidemiológica de la encefalitis viral, así como en el manejo del paciente ya que se describen hallazgos clínicos importante en la población adulta estudiada.(AU)
Subject(s)
Humans , Cerebrospinal Fluid/virology , Encephalitis, Herpes Simplex/epidemiology , Epidemiological Monitoring , Herpesviridae/isolation & purification , Epidemiology, Descriptive , Longitudinal Studies , Colombia/epidemiologyABSTRACT
Objective To establish an epidemiological surveillance of viral herpes encephalitis in major hospitals of Monteria, Cordoba. Methods From September 2009 to December 2011, a descriptive study of cases of viral encephalitis was made in three hospitals in the city of Monteria. Cerebrospinal fluid (CSF) samples from 118 patients were included in the study. Clinical aspects, as well as cytochemical and microbiological analysis (Gram stain and culture) of CSF, were used for selecting the patients. Virus detection was performed by using multiplex nested PCR for Herpes simplex virus 1 and 2, Epstein Barr virus, Cytomegalovirus and Varicella zoster virus. Results Viral DNA of herpesvirus was detected in the CSFs of 30 (25.4 %) participants, as follows: 22 (18.6 %) Herpes simplex 1 and 2 viruses, 4 (3.3 %) Cytomegalovirus and 1 (0.8 %) Varicella zoster virus. Co-infections were observed in 3 patients (2.5 %), 1 case by HSV-VZV and 2 cases by CMV/HSV. The clinical manifestations of the patients included: headache (18.6 %), fever (14.4 %), asthenia (10.1 %), seizures (9.3 %), vomiting (8.4 %), and stiff neck (5.9 %). Thirty percent of the patients also had HIV-AIDS. A case fatality rate of 20 % was observed for the patients. Conclusions This paper shows that herpesvirus is a cause of infection of the CNS in patients from Cordoba. This study contributes to the epidemiology of encephalitis, as well as to patient management.