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RESUMEN El dengue es una infección viral aguda transmitida por la picadura de mosquitos del género Aedes, la cual produce hasta 100 millones de infecciones anuales en el mundo. Una gran proporción de individuos infectados con el virus presentan infecciones asintomáticas. Sin embargo, de los individuos que desarrollan la enfermedad, el 95 % presentan signos y síntomas similares a una virosis común, que por lo general se autoresuelven (dengue con y sin signos de alarma). El 5 % restante puede evolucionar a manifestaciones graves, caracterizadas por hemorragias, daño orgánico, choque hipovolémico e incluso la muerte (dengue grave). Los monocitos son uno de los blancos principales de la infección producida por el virus del dengue (DENV), los cuales participan en la replicación del mismo y en la producción de una gran variedad de citoquinas que contribuyen con el daño de diferentes tejidos y órganos en respuesta a la infección. Los monocitos se dividen en tres subpoblaciones: clásica (CD14++CD16-), no clásica (CD14+CD16++) e intermedia (CD14++CD16+), las cuales poseen respuestas funcionales contrastantes en diferentes procesos inflamatorios, en cuanto a la producción de mediadores solubles e interacción con el endotelio. Los monocitos no clásicos parecen ser los principales productores de mediadores inflamatorios como el TNF-α y la IL-1β en respuesta a la infección por DENV. Por lo tanto, se propone que cada subpoblación de monocitos debe tener un papel diferencial en la inmunopatología de la enfermedad. En esta revisión se recopilan los principales aspectos de la replicación viral y la inmunopatología del dengue, así como los principales hallazgos referentes al papel de los monocitos en esta infección y además, se propone un papel potencial y diferencial de las subpoblaciones de monocitos. SUMMARY Dengue is an acute viral infection transmitted by the bite of the mosquito belonging to the genus Aedes, which produce until 100 millions of infections worldwide per year. A high proportion of infected individuals develop an asyntomatic infection. Nevertheless, among patients that develop a clinical disease, 95 % of them show clinical signs and symptoms similar to common virosis, that in the most of the cases can recover by themselves (dengue with and without alarm signs); the remaining 5 % can evolve to severe manifestations, characterized for hemorrhages, organic damage, hypovolemic shock and death (severe dengue). Monocytes are one of the main targets of the infection by dengue virus (DENV), supporting the viral replication, contributing to the production of high levels of cytokine and the damage of different tissues and organs in response to the infection. Monocytes are divided in 3 subsets: classical (CD14++CD16-), non-classical (CD14+CD16++) and intermediate (CD14++CD16+); which have differential functional responses in the inflammatory process, regarding the production of inflammatory mediators and the interaction with the endothelium. The non-classic monocytes seem to be the main producers of inflammatory mediators such as TNF-α and IL-1β in response to DENV infection. Therefore, it is proposed that each monocyte subset may have a different role in the disease immunopathology. This review collect the main evidence regarding the viral replication and the immunopathology of dengue, also it shows the most important findings about the role of monocytes in this infection and proposes a potential differential involvement of monocytes subsets.

The current Ebola outbreak is the largest, longest, and most complex the world has ever seen, that is, the United Nations declared it “a threat to peace and security”1 and the World Health Organization acknowledged it to be a Public Health Emergency of International Concern. As new evidence emerges2 to enlighten the clinical characteristics and the prognosis of the acute phase of the disease, there is relatively scarce information about the convalescent phase, especially the measures to control the sexual transmission of Ebola. In order to assess the evidence that underlies the current recommendation (use of condom for 3 months in convalescent male3), we performed a systematic search of the literature (for articles indexed in Medline and Embase) using the following MESH terms (Ebolavirus; Hemorrhagic Fever, Ebola; Semen) with no further restrictions (Table 1).

Regulatory T cells (Tregs) inhibit the activation of the immune response which could down-regulate the systemic and focal activation observed during ischemic stroke. In fact, in animal models, Tregs infiltrate the infarcted brain and reduce the pro-inflammatory cytokine production and infarct volume, mainly in late stages of ischemia. Recently, an expansion and greater suppressive capacity of circulating Tregs after treatment with statins was observed, in addition to their cardio- and neuroprotective actions demonstrated previously. Thus, to determine whether Treg modulation mediated by statins can also be beneficial during stroke, cerebral ischemia was artificially induced in Wistar rats by transient middle cerebral artery occlusion (tMCAO) during 60 minutes with subsequent reperfusion for 7 days. Six hours after surgery, some animals were treated with atorvastatin (ATV, 10 mg/kg) or carboxymethylcellulose as vehicle at the same concentration every other day during 7 days. Some animals were sham operated as control group of surgery. Interestingly, ATV treatment prevented the development of infarct volume, reduced the neurological deficits, and the circulating and cervical lymph node CD25+FoxP3+ Treg population. Moreover, there was a reduction of glial cell activation, which correlated with decreased circulating Tregs. Remarkably, treatment with ATV induced an increase in the frequency of CD4+CD25+ T cells, in particular of those expressing CTLA-4, in brain samples. Together, these results suggest that ATV can modulate Tregs in peripheral tissue and favor their accumulation in the brain, where they can exert neuroprotective actions maybe by the reduction of glial cell activation.

Numerous reports have focused on consensus peptides to determine CD8+ T-cell responses; however, few studies evaluated the functional profile using peptides derived from circulating strains of a specific region. We determined the effector profile and maturation phenotype of CD8+ T-cells targeting the consensus APPEESFRS (AS9) epitope and its variant APPEESFRF (AF9), previously identified. The free energy of binding, maturation phenotype, and polyfunctional profile of both peptides were similar. The magnitude of CD8+ T-cell responses to AF9 was greater than the one elicited by AS9, although the difference was not significant. The polyfunctional profile of AF9 was characterized by CD107a/interleukin-2 (IL-2)/macrophage inflammatory protein beta (MIP1β) and by interferon gamma (IFNγ)/MIP1β/tumor necrosis factor alpha (TNFα) in response to AS9. TNFα production was significantly higher in response to AF9 than to AS9, and there was a negative correlation between the absolute number of CD8+ T-cell-producing TNFα and the plasma human immunodeficiency virus (HIV) load, suggesting a role of this cytokine in the control of HIV replication.

In this opinion article we consider the possibility that human spermatozoa have receptors for human immunodeficiency virus-1 (HIV-1). It is clear that sperm cells have the potential for transmitting HIV-1, but the mechanisms responsible for spreading or the virus by this vector are not known. In contrast to the traditional HIV-1 target cells, spermatozoa do not express CD4 receptors or the CCR5/CXCR4 co-receptors. Recent evidence indicates that astrocytes, which also do not express these molecules, can be infected with HIV-1 through the mannose receptor. Furthermore, a 160-kDa sperm receptor that interacts with the HIV gp 120 has been described. Therefore, we hypothesize that the mannose receptor, of 165-175 kDa, is the receptor that HIV-1 uses to invade spermatozoa, which could lead to both vertical and horizontal transmission of HIV-1.

One of the main characteristics of the human immunodeficiency virus is its genetic variability and rapid adaptation to changing environmental conditions. This variability, resulting from the lack of proofreading activity of the viral reverse transcriptase, generates mutations that could be fixed either by random genetic drift or by positive selection. Among the forces driving positive selection are antiretroviral therapy and CD8+ T-cells, the most important immune mechanism involved in viral control. Here, we describe mutations induced by these selective forces acting on the pol gene of HIV in a group of infected individuals. We used Maximum Likelihood analyses of the ratio of non-synonymous to synonymous mutations per site (dN/dS) to study the extent of positive selection in the protease and the reverse transcriptase, using 614 viral sequences from Colombian patients. We also performed computational approaches, docking and algorithmic analyses, to assess whether the positively selected mutations affected binding to the HLA molecules. We found 19 positively-selected codons in drug resistance-associated sites and 22 located within CD8+ T-cell epitopes. A high percentage of mutations in these epitopes has not been previously reported. According to the docking analyses only one of those mutations affected HLA binding. However, algorithmic methods predicted a decrease in the affinity for the HLA molecule in seven mutated peptides. The bioinformatics strategies described here are useful to identify putative positively selected mutations associated with immune escape but should be complemented with an experimental approach to define the impact of these mutations on the functional profile of the CD8+ T-cells.

Objective : To determine the ability of supervised neuronal networks at making the appropriate classification of fertile and infertile men using conventional seminal parameters. Materials and methods: Cross-sectional study assembled on the database of the Universidad de Antioquia Reproduction Group, with a selection of men experiencing reproductive problems within the previous 12 months, and men with a history of having had children. Convenience sampling. The data considered were age, time of sexual abstinence, ejaculate volume, pH, percentage of sperm motility, viability and concentration. Using a supervised neuronal network, a training model and a validation model were created. Results : Overall, 204 men were included, 129 for the training model, 35 for validation, 40 for testing the model and 25 for external validation. The neuronal network model made the correct classification of 90% of the subjects with reproductive problems, and 91% of the fertile subjects. In the validation model, the neuronal network made the correct classification of 40% of the subjects with reproductive problems, and 100% of the fertile subjects. Conclusion : Neuronal networks emerge as a technology that may prove to be valuable for the study of male infertility. More rigorous evaluations are required in order to determine their true usefulness in the study of infertile couples.

RESUMEN: Se considera que la sepsis es la principal causa de mortalidad en las unidades de cuidado intensivo, por lo cual ha sido objeto de numerosas investigaciones que aún no se han traducido en avances terapéuticos significativos. El balance entre los fenómenos proinflamatorios y antiinflamatorios característicos de este síndrome es el que puede determinar el desenlace del paciente; además, la complejidad del desarrollo de estrategias terapéuticas en sepsis está relacionada con la naturaleza heterogénea de la respuesta inmune; se destaca la importancia de los factores genéticos que regulan el componente inmune durante la respuesta inflamatoria. Con base en tales conocimientos, esta revisión se centra en genes de citocinas importantes en el curso clínico de la sepsis, en la información sobre sus variantes genéticas en la población con sepsis y en su impacto sobre la función del gen. Estos factores son de importancia crítica y un mejor conocimiento acerca de ellos podría ayudar a evaluar el riesgo de desarrollar sepsis y a definir su asociación con la evolución clínica de este síndrome. ABSTRACT: Sepsis is the main cause of mortality in intensive care units. Therefore, many efforts to develop therapeutic approaches have been made without significant progress. The balance between the pro-inflammatory and anti-inflammatory responses during the course of sepsis may determine the clinical outcome of patients; besides, the complexity of developing successful treatments in sepsis may be related to the heterogeneous nature of immune responses; the importance of genetic factors that regulate the immune component during the inflammatory response is emphasized. Based on such facts, this review focuses on genes of cytokines involved in the clinical course of sepsis; on information about their allelic variants found in the population with sepsis, and on their impact on gene expression. These factors are of critical importance, and a better knowledge about them could help to evaluate the risk of developing sepsis, and to define their association with the clinical evolution of this syndrome.

The clinical course of infection with human immunodeficiency virus type-1 (HIV-1) is a variable and complex process that depends on viral and host components. In the majority of infected individuals, the immune response is generated from the initial phases of infection, achieving the control of the viral replication through innate effector mechanisms, neutralizing specific antibodies and particularly through cytotoxic CD8+T cell activity. Despite the generation of these specific cellular and humoral responses, it becomes ineffective in chronic stages of infection because of changes in viral peptide targets, the low fidelity of the reverse transcriptase and the immune pressure. During the activation of CD8+ T cells, the signal delivered by the viral peptide presented in the context of the class I major histocompatibility complex (MHC-I) molecules, is essential. Correlation studies between the MHC-I and the resistance/ susceptibility (R/S) to HIV infection have focused on four aspects, namely: 1) the expression of specific alleles; 4) the degree of homozygosity/heterozygosity; 3) the degree of exposure to different alloantigens; 4) the relation with KIR receptors. In this review, we focus on resistance/susceptibility to HIV-1 infection, particularly related to the MHC, hoping to have a better understanding of this phenomenon that may allow the development of novel therapeutic intervention tools. RESUMEN: El curso clínico de la infección por el virus de inmunodeficiencia humana tipo 1 es un proceso variable y complejo que depende de componentes virales y del hospedero. En la mayoría de los individuos infectados, la respuesta inmune generada en las fases iniciales de la infección logra controlar la replicación viral por mecanismos efectores innatos, de anticuerpos neutralizantes específicos y particularmente de la actividad de los linfocitos T CD8+ (LT CD8+). A pesar de generarse una respuesta inmune específica, esta se vuelve ineficaz en las etapas crónicas de la infección debido a cambios en los péptidos virales blanco, los cuales conducen a una pérdida del reconocimiento del antígeno presentado; dichos cambios son dados por la baja fidelidad de la transcriptasa reversa y la selección de cuasi-especies por la presión inmunológica. Durante la activación de los LT CD8+ es importante la señal ejercida por el péptido viral, el cual se presenta en el contexto de una molécula del complejo mayor de histocompatibilidad clase I (CMH-I). Estudios de correlación entre el CMH-I y la resistencia/susceptibilidad (R/S) al VIH se han centrado en cuatro aspectos: 1) la expresión de alelos específicos; 2) el grado de homocigocidad/heterocigocidad; 3) la exposición a diversos aloantígenos; 4) la relación con receptores KIR. En esta revisión se aborda el fenómeno de resistencia/susceptibilidad a la infección por el VIH-I relacionado con el CMH-I, cuyo entendimiento favorecerá el desarrollo de herramientas novedosas de intervención terapéutica.

Statins are a group of drugs that inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, which limits cholesterol synthesis and production of isoprenoid compounds, phenomena responsible for the reduction of atherosclerotic disease in individuals with hypercholesterolemia. Due to the wide prescription and use of these drugs, some additional beneficial effects have been observed in various clinical settings, mainly related to the decreased production of isoprenoid compounds. Some of these effects have been associated with the modulation of the immune system, but their effect on regulatory T cells (Treg) has not been well studied, despite the fact these cells are crucial to regulate the intensity of the immune response and to preserve immune homeostasis. This review focuses on the common pathways through which statins and Treg cells interact to regulate the immune response. Although the results from early investigations show that statins increase the frequency and suppressive capacity of Treg cells, further research is required to determine whether that relationship produces beneficial or harmful consequences for the immune regulation in different clinical settings. RESUMEN: Las estatinas constituyen un grupo de fármacos inhibidores de la enzima 3-hidroxi-3- metilglutaril-coenzima A reductasa, que limitan la síntesis de colesterol y la producción de compuestos isoprenoides, fenómenos responsables de la reducción de la enfermedad aterosclerótica en individuos con hipercolesterolemia. Debido a la amplia prescripción y uso de estos fármacos, se han observado efectos benéficos adicionales, relacionados principalmente con la disminución de la síntesis de compuestos isoprenoides. Parte de estos efectos se asocia con la modulación del sistema inmune; sin embargo, su acción sobre las células T reguladoras (Treg) ha sido poco estudiada, a pesar de que estas células son fundamentales para regular la intensidad de la respuesta inmune y mantener la homeostasis inmunológica. En esta revisión abordamos las vías comunes por las cuales las estatinas y las células Treg pueden interactuar para regular la respuesta inmune. Aunque los resultados de las primeras investigaciones muestran que las estatinas aumentan la frecuencia y, posiblemente, la capacidad supresora de las células Treg, se requieren más estudios que permitan dilucidar si esta relación tiene consecuencias benéficas o perjudiciales para la regulación inmune, en diferentes contextos clínicos.

La infección por el VIH se asocia con una inmunodeficiencia secundaria grave que lleva a la aparición de infecciones oportunistas y procesos oncogénicos. En el curso de esta infección se observan comúnmente alteraciones de la inmunidad mediada por células T y células presentadoras de antígeno; en la actualidad se considera que ciertas poblaciones celulares con propiedades inmunorreguladoras son en parte responsables de estas alteraciones. De hecho, en los principales sitios de replicación viral, como los órganos linfoides y el tejido linfoide asociado a la mucosa gastrointestinal, se han observado alteraciones funcionales y cuantitativas en la subpoblación de células T reguladoras (Treg). Aunque se desconoce el papel de estas células en la patogénesis de la infección por el VIH, los estudios sugieren que podría ser dual: 1) proteger del daño tisular y de la eliminación de células T CD4+ causados por la hiperactivación inmunológica; 2) contribuir a la patogénesis de esta infección viral. La acumulación de células Treg funcionales afecta el desarrollo de respuestas inmunes específicas que permiten la eliminación del patógeno, facilitando de esta manera su permanencia en los tejidos. En esta revisión se presenta la evidencia científica disponible sobre el efecto de las células Treg en la patogénesis de la infección por el VIH.