Semen promotes the differentiation of tolerogenic dendritic cells.

Seminal plasma is not just a carrier for spermatozoa. It contains high concentrations of cytokines, chemokines, and other biological compounds that are able to exert potent effects on the immune system of the receptive partner. Previous studies have shown that semen induces an acute inflammatory response at the female genital mucosa after coitus. Moreover, it induces regulatory mechanisms that allow the fetus (a semiallograft) to grow and develop in the uterus. The mechanisms underlying these regulatory mechanisms, however, are poorly understood. In this study, we show that seminal plasma redirects the differentiation of human dendritic cells (DCs) toward a regulatory profile. DCs differentiated from human monocytes in the presence of high dilutions of seminal plasma did not express CD1a but showed high levels of CD14. They were unable to develop a fully mature phenotype in response to LPS, TNF-α, CD40L, Pam2CSK4 (TLR2/6 agonist), or Pam3CSK4 (TLR1/2 agonist). Upon activation, they produced low amounts of the inflammatory cytokines IL-12p70, IL-1ß, TNF-α, and IL-6, but expressed a high ability to produce IL-10 and TGF-ß. Inhibition of the PG receptors E-prostanoid receptors 2 and 4 prevented the tolerogenic effect induced by seminal plasma on the phenotype and function of DCs, suggesting that E-series PGs play a major role. By promoting a tolerogenic profile in DCs, seminal plasma might favor fertility, but might also compromise the capacity of the receptive partner to mount an effective immune response against sexually transmitted pathogens.

Low extracellular pH stimulates the production of IL-1ß by human monocytes.

The development of acidic environments is a hallmark of inflammatory processes of different etiology. We have previously shown that transient exposure to acidic conditions, similar to those encountered in vivo, induces the activation of neutrophils and the phenotypic maturation of dendritic cells. We here report that extracellular acidosis (pH 6.5) selectively stimulates the production and the secretion of IL-1ß by human monocytes without affecting the production of TNF-α, IL-6 and the expression of CD40, CD80, CD86, and HLA-DR. Stimulation of IL-1ß production by pH 6.5-treated monocytes was shown to be dependent on caspase-1 activity, and it was also observed using peripheral blood mononuclear cells instead of isolated monocytes. Contrasting with the results in monocytes, we found that pH 6.5 did not stimulate any production of IL-1ß by macrophages. Changes in intracellular pH seem to be involved in the stimulation of IL-1ß production. In fact, monocytes cultured at pH 6.5 undergo a fall in the values of intracellular pH while the inhibitor of the Na+/H+ exchanger, 5-(N-ethyl-N-isopropyl)amiloride induced both, a decrease in the values of intracellular pH and the stimulation of IL-1ß production. Real time quantitative PCR assays indicated that monocytes cultured either at pH 6.5 or in the presence of 5-(N-ethyl-N-isopropyl)amiloride expressed higher levels of pro-IL-1ß mRNA suggesting that low values of intracellular pH enhance the production of IL-1ß, at least in part, by stimulating the synthesis of its precursor.

New insights into the mechanisms controlling neutrophil survival.

PURPOSE OF REVIEW: Neutrophil survival is regulated by a complex convergence of different pathways. The present review analyzes these pathways and discusses how neutrophil survival is modulated during the course of inflammatory reactions. RECENT FINDINGS: Although apoptosis appears to be the predominant cell death pathway in the neutrophil, recent data reveal that neutrophil survival is also regulated by a number of nonconventional pathways including NETosis, autophagic cell death, and other less characterized mechanisms. This supports an even more complex picture of the mechanisms involved in the regulation of neutrophil survival than previously thought. SUMMARY: The control of neutrophil survival is central to homoeostasis and resolution of inflammation. Cell death is usually discussed dichotomously in terms of apoptosis or necrosis. There are two main pathways responsible for the stimulation of apoptosis; a death receptor pathway triggered by Fas, tumor necrosis factor alpha, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and a mitochondrial pathway stimulated by a number of stressors such as DNA damage, growth factor deprivation, and chemotherapy drugs. Nonconventional pathways of neutrophil death include NETosis and autophagic cell death as well as a number of poorly characterized mechanisms. Understanding the integrated pathways responsible for the control of neutrophil survival holds therapeutic promise in infectious and inflammatory diseases.

Dental beliefs in HIV+ patients with different oral health care needs.

The aim of this work was to assess the score variation of scales 1 and 2 of the DCBS (Dental Coping Beliefs Scale) of beliefs on oral health regarding oral health needs, clinical progression of the viral infection, medical care needs, age and gender in HIV+ patients. The DCBS was randomly administered to 102 HIV+ patients at the "Juan A. Fernandez Hospital", Buenos Aires, Argentina. For each of the 29 items, patients indicated their responses on a five point scale ranging from "strongly disagree" to "strongly agree". Oral health needs were assessed through the CCITN (Community Caries Index of Treatment Need) and the CPITN (Community Periodontal Index of Treatment Need). Data on CD4 cell count, pharyngeal-esophageal candidiasis, tuberculosis, pneumonia and hospitalization because of HIV-related opportunistic diseases were recorded. A linear regression model was built in which the number of items reporting wrong dental beliefs was the dependent variable and the remaining variables were independent. Altogether 65.7% were male (36.0 +/- 0.87 y.o.) and 34.3% were female (36.11 +/- 1.21 y.o.) patients. The eight independent variables were significant for the model (F(8.93)= 93.20, p < 0.05; R = 0.80). The estimated parameters were all positive except for CD4 cell counts. The results demonstrate that the DCBS was useful to identify HIV+ patients as a caries and periodontal disease risk group because of their wrong dental beliefs and suggests the need of dental education interventions.

Resistencia antibiótica y aspectos clínicos de Neisseria gonorrhoeae anorrectal en un hospital de CABA, Argentina / Antimicrobial resistance and clinical aspects in anorectal Neisseria gonorrhoeae in a hospital in CABA, Argentina

La infección por Neisseria gonorrhoeae (NG) es considerada de alta prioridad en salud pública, por su capacidad para desarrollar resistencia a la mayoría de los antibióticos empleados para tratarla. La presentación anorrectal suele ser asintomática y frecuente en hombres que tienen sexo con hombres (HSH). En Argentina, se recomienda terapia antibiótica dual (ceftriaxona+azitromicina/doxiciclina) como primera línea empírica. Este estudio observacional y retrospectivo se realizó para evaluar el porcentaje de positividad de NG anorrectal, el perfil de sensibilidad a penicilina, tetraciclina, ciprofloxacina, ceftriaxona, cefixima y azitromicina, así como los aspectos clínicos-epidemiológicos de los pacientes atendidos entre 20/10/2015 y 20/03/2020 en consultorios coloproctológicos de un hospital público. Se detectaron 55/436 hisopados rectales positivos para NG (13%). El 95% era HSH y 71%, VIH+. En 18/55 NG fue la única infección. Las co-infecciones más frecuentes: HPV (38%) y C. trachomatis (35%). La sensibilidad a cefalosporinas de espectro extendido (CEE) y a azitromicina fueron 100% y 98%, respectivamente. Se observó la emergencia local de los primeros cinco aislamientos de NG anorrectal con sensibilidad reducida (SR) a CEE, el primer aislamiento con categoría no-sensible a azitromicina y otro con SR a azitromicina concomitantemente con SR a CEE. Aunque el uso de terapia empírica dual sigue siendo adecuado para nuestra institución, se observó la emergencia de aislamientos con SR y NS a las drogas de primera línea, evidenciando la importancia de la vigilancia epidemiológica a nivel local para definir los tratamientos empíricos.

Neisseria gonorrhoeae (NG) infection is considered a high public health priority because of its ability to develop resistance to most of the antibiotics used to treat it.The anorectal presentation is generally asymptomatic and frequent in men who have sex with men (MSM). In Argentina, dual therapy (ceftriaxone+azithromycin/doxycycline) is recommended as first line empiric therapy.This observational and retrospective study was conducted to evaluate the percentage of anorectal NG positivity, the susceptibility profile to penicillin, tetracycline, ciprofloxacin, ceftriaxone, cefixime and azithromycin, as well as the clinical-epidemiological aspects of patients attended between 20/10/2015 and 20/03/2020 in coloproctology of a public hospital.We detected 55/436 positive rectal swabs for NG (13%). 95% were MSM and 71% were PLHIV. In 18/55 NG was the only infection. The most frequent co-infections: HPV (38%) and C. trachomatis (35%).Susceptibility to extended-spectrum cephalosporins (ESCs) and azithromycin was 100% and 98%, respectively. Local emergence of the first five anorectal NG isolates with decreased susceptibility (DS) to ESCs, the first isolate with nonsusceptible category to azithromycin and another with DS to azithromycin concomitantly with DS to ESCs were observed.Although the use of dual empirical therapy continues to be adequate for our institution, the emergence of isolates with DS and NS to first-line drugs was observed, evidencing the importance of epidemiological surveillance at the local level to define empirical treatments

Chemsex y uso de sustancias durante las relaciones sexuales: resultados de una encuesta realizada en Argentina / Chemsex and use of substances during sexual intercourse: results of a survey conducted in Argentina

Introducción: Chemsex está relacionado con el uso de ciertas drogas que facilitan la excitación y el prolongar la duración de los encuentros sexuales.Objetivo: Describir el perfil de consumo de los usuarios de sustancias durante las relaciones sexuales (SRS) y su relación con variables demográficas, de estilo de vida y de salud.Métodos: Estudio descriptivo y transversal realizado a través de una encuesta autoadministrada y anónima en el marco de la plataforma Google Forms® que se transmitió en diferentes redes sociales. Objetivo: describir los aspectos demográficos y de estilo de vida de los encuestados y del subgrupo de usuarios de SRS y chemsex.Resultados: Se recibieron 2924 encuestas; 421 personas (16,9%) refirieron haber consumido al menos una vez uno o más de los siguientes: mefedrona, metanfetamina, crystal meth, GHB/GBL, cocaína, LSD, poppers, ketamina y éxtasis. Chemsex se definió como el consumo de los tres primeros y su prevalencia fue del 1,1%. El perfil de usuario de SRS y chemsex en nuestro estudio fue un hombre de entre 26 y 35 años, HSH y habitante de la Ciudad de Buenos Aires. Hubo mayor proporción de personas con VIH y diagnósticos de ITS en el último año dentro de los usuarios de SRS y chemsex.Conclusiones: Esta es la primera encuesta que trata este tema en nuestro país y en América Latina. Teniendo en cuenta la tendencia a un menor uso de los condones RESUMENARTÍCULO ORIGINALISSN 2314-3193. Actualizaciones en sida e infectología. Buenos Aires. noviembre 2020. volumen 28. número 103: 40-50y a presentar más diagnósticos de ITS y VIH en la población de usuarios de SRS, consideramos de interés conocer la epidemiología en nuestra población

Introduction: Chemsex is related to the use of certain drugs to facilitate sustained arousal and induce a feeling of instant rapport with sexual partners.Aim: To describe the consumption profile of users of substances during sexual intercourse (SSI) and its relationship with demographic, lifestyle and health variables.Methods: Descriptive and cross-sectional study conducted through a self-administered and anonymous survey under the Google Forms platform ® which was broadcasted on different social networks. Main outcome measures: Description on demographic and lifestyle aspects of the respondents and in the subgroup of SSI and chemsex users.Results: 2924 surveys were received; 421 people (16.9%) referred to having consumed at least once one or more of the following: mephedrone, crystal meth, GHB/GBL, cocaine, LSD, poppers, ketamine and ecstasy. Chemsex was defined as the consumption of the first three and its prevalence was 1.1%. A SSI and chemsex user profile in our study was a man between 26 and 35 years, MSM and inhabitant of the city of Buenos Aires. SSI and chemsex users were more likely to and STI in the last year and to have HIV diagnosis.Conclusions: This is the first survey that deals with this issue in our country and in Latin America. Accounting for the tendency to less use of condoms and to present more diagnoses of STIs and HIV in the population of SSI users, we consider it necessary to study this subject in our country as the rising reports in world literature show a boost in substance use.Keywords: Chemsex, Drugs, HIV, VIH, STI, ITS.Chemsex and use of substances during sexual intercourse: results of a survey conducted in Argentina

Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate.

During the late stages of the HIV-1 replication cycle, the viral polyprotein Pr55(Gag) is recruited to the plasma membrane (PM), where it binds phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and directs HIV-1 assembly. We show that Rab27a controls the trafficking of late endosomes carrying phosphatidylinositol 4-kinase type 2 α (PI4KIIα) toward the PM of CD4(+) T cells. Hence, Rab27a promotes high levels of PM phosphatidylinositol 4-phosphate and the localized production of PI(4,5)P2, therefore controlling Pr55(Gag) membrane association. Rab27a also controls PI(4,5)P2 levels at the virus-containing compartments of macrophages. By screening Rab27a effectors, we identified that Slp2a, Slp3, and Slac2b are required for the association of Pr55(Gag) with the PM and that Slp2a cooperates with Rab27a in the recruitment of PI4KIIα to the PM. We conclude that by directing the trafficking of PI4KIIα-positive endosomes toward the PM, Rab27a controls PI(4,5)P2 production and, consequently, HIV-1 replication.

Sífilis anorrectal: una entidad subdiagnosticada. Casuística de un hospital público de la Ciudad Autónoma de Buenos Aires / Anorectal syphilis: an underdiagnosticated entity. Casuistry of a public hospital in the autonomous city of Buenos Aires

Introducción: Las infecciones de transmisión sexual (ITS) afectan anualmente a millones de personas. La sífilis aumenta tanto a nivel mundial como nacional. El sexo anorreceptivo es factor predisponente y hombres que tienen sexo con hombres (HSH) son vulnerables. Las lesiones anales en estadio primario provocan intensa proctalgia y en estadio secundario pueden simular condilomas virales, que si resuelven espontáneamente quedan sin diagnóstico etiológico. Métodos: Estudio descriptivo, ambispectivo, transversal. Revisión de registros de pacientes atendidos en coloproctología del Hospital Fernández (01/01/2015 - 01/03/2019). Se incluyeron pacientes con serología confirmatoria. Variables analizadas: sexo, edad, diagnóstico de derivación, HIV, otras ITS, sexo anal/oro-anal, estadio, clínica y casos/año.Resultados: Setenta y siete casos (61 hombres, 12 mujeres, 4 mujeres trans). Edad mediana: 30 años (rango: 18 - 72), 48% <30 años, 83% no utilizó preservativo (100% de los HIV+). Diecisiete casos (22%) detectados durante pesquisa de Chlamydia. Cincuenta y ocho pacientes (75%) presentaron ITS asociada. Coexistieron sífilis, HIV y linfogranuloma venéreo (LGV) en 8 HSH. Manifestaciones observadas: proctalgia (77%), proctorragia (55%), secreción (53%) y úlcera anal (51%). 50% de mujeres llegaron con diagnóstico erróneo. Casos/año: 6 en 2015, 13 en 2016, 21 en 2017, 31 en 2018 y 6 en primer bimestre de 2019.Conclusiones: Se detectó aumento progresivo de casos de sífilis anorrectal (mayormente en HSH), que aun siendo HIV+ no usa preservativo. Actualmente debe sospecharse asociación de sífilis con LGV en HSH HIV+. La similitud clínica con patologías no venéreas y la remisión espontánea de lesiones obliga a testearla para evitar su progresión y cortar la cadena de contactos.

Introduction: STIs affect millions of people annually. Syphilis increases both globally and nationally. Anoreceptive sex is a predisposing factor and men who have sex with men (MSM) are vulnerable. The anal lesions in primary stage cause in-tense proctalgia and in secondary stage they can simulate viral condylomas, that if they resolve spontaneously might remain without etiological diagnosis.Methods: Descriptive, ambispective, cross-sectional study. Review of records of patients seen in coloproctology at the Fernández Hospital (01/01/2015 - 03/01/2019). Patients with confirmatory serology were included. Variables ana-lyzed: sex, age, derivation diagnosis, HIV, other STDs, anal sex / oro-anal, stage, clinic and cases/year.Results: Seventy-seven cases (61 men, 12 women, 4 trans-women). Mean age of 30 years (range: 18 - 72), 48% <30 years. 83% did not use condoms (100% of HIV +). Sev-enteen cases (22%) detected during Chlamydia search. Fif-ty-eight patients (75%) had associated STIs. Syphilis, HIV and LGV coexisted in 8 MSM. Manifestations observed: proctalgia (77%), proctorrhagia (55%), discharge (53%), anal ulcer (51%). 50% of women arrived with inacurate diagnosis. Cases/year: 6 in 2015, 13 in 2016, 21 in 2017, 31 in 2018 and 6 in the first two months of 2019.Conclusions: There was a progressive increase in cases of anorectal syphilis (mostly MSM), that even when they are HIV +, does not use a condom. Currently, association of syphilis with LGV in MSM HIV + should be suspected. The clinical similarity with non-venereal pathologies and the spontaneous remission of lesions obliges to test it to avoid its progression and to break the chain of transmission

Proctitis infecciosa por Chlamydia Trachomatis / Infectious proctitis by Chlamydia Trachomatis

Introducción: Las infecciones transmisibles sexualmente (ITS) son motivo de consulta frecuente, encontrándose Chlamydia trachomatis (CT) entre las prevalentes. Este germen provoca proctitis de diversa gravedad según el biovar involucrado. Los casos más floridos suelen ser ocasionados por el biovar LGV, responsable de la entidad linfogranuloma venéreo. Se desconocen la prevalencia de CT como causa de proctitis en Argentina y los biovares implicados. Con el objetivo de estudiar estas variables, se diseñó un protocolo para detectar y genotipificar CT en pacientes con proctitis infecciosa. Pacientes y métodos: Se incluyeron pacientes mayores de 18 años con cuadro de proctitis infecciosa atendidos en un centro público y otro privado. Se excluyeron pacientes con enfermedad inflamatoria intestinal y radioterapia pelviana. El estudio fue aprobado por un Comité de Ética y los pacientes firmaron un consentimiento informado. En las muestras de hisopado anal se realizó detección y tipificación molecular de CT. Resultados: Entre 31de agosto de 2017 y 31 de mayo de 2018, se incluyeron 56 pacientes (1 mujer, 53 hombres, 2 mujeres trans), 79% HIV+. En 29 casos (52%) se detectó CT. Todos eran hombres que tienen sexo con hombres (HSH) y refirieron practicar sexo anal u oral receptivo no protegido. La mediana de edad de este subgrupo fue de 31 años; 83% HIV+ en tratamiento antirretroviral y mediana de CD4 637 cel/mm3. La coinfección con otras ITS fue del 41% (siendo las más frecuentes HPV, gonococia y sífilis). Los motivos de consulta más frecuentes fueron proctorragia, pujo y tenesmo, proctalgia y secreción. Las manifestaciones clínicas fueron variadas: proctitis, úlcera perianal, tumor endoanal/rectal y absceso/fístula. El 86% de las proctitis correspondió al biovar LGV, siendo 62% moderadas a graves. La mediana de tiempo de evolución hasta el diagnóstico fue 21 días. Los casos más prolongados correspondieron a cuadros clínicos y endoscópicos más graves. La duración del tratamiento se adecuó al biovar involucrado. Todos los pacientes respondieron favorablemente; sin embargo, las dos fístulas perianales requirieron resolución quirúrgica. Conclusiones: Proctitis, úlceras y fístulas son manifestaciones inespecíficas; el hallazgo clínico y endoscópico per se no son suficientes para definir la etiología; sólo una anamnesis minuciosa permite presumir una ITS como agente causal. La tipificación logra definir el biovar, dato fundamental para adecuar el tratamiento, cortar la cadena de transmisión y contar con datos epidemiológicos a nivel local. Como resultado de esta investigación, el Ministerio de Salud de Nación proyectó la emisión de una alerta sobre la presencia de LGV en nuestro medio. Tipo de estudio: Observacional, transversal, analítico, multicéntrico.

Introduction: Sexually transmitted infections (STI) are a frequent reason for consultation, being Chlamydia trachomatis (CT) among the most prevalent ones. It causes proctitis of varying severity depending on the biovar involved. The most severe cases are usually caused by the LGV biovar, responsible for the entity called lymphogranuloma venereum. The prevalence of CT as a cause of proctitis in Argentina and the biovars involved are unknown. In order to study these variables, a protocol was designed to detect and genotype CT in patients with infectious proctitis. Patients and methods: Patients over 18 years old with infectious proctitis were attended in a public and private center. Patients with inflammatory bowel disease and pelvic radiation therapy were excluded. The study was approved by an Ethics Committee and the patients signed an informed consent. The detection and molecular typing of CT was performed in anal swab samples. Results: Between 31-08-2017 and 31-05-2018, 56 patients were included (1 woman, 53 men, 2 trans women), 79% HIV +. In 29 cases (52%) CT was detected. All were MSM and reported to practice unprotected receptive oral or anal sex. The median age of this subgroup was 31 years; 83% HIV + on antiretroviral treatment and median CD4 637 cel / mm3. The coinfection with other STIs was present 41% (the most frequent were HPV, gonococcal and syphilis). The most frequent symptoms were bleeding, tenesmus, proctalgia and secretion. The clinical manifestations were varied: proctitis, perianal ulcer, endoanal / rectal tumor and abscess / anal fistula. 86% of the proctitis corresponded to the LGV biovar, being 62% moderate to severe. The median time of evolution until the diagnosis was 21 days. The most prolonged cases corresponded to more severe clinical and endoscopic symptoms. The duration of the treatment was adapted to the biovar involved. All patients responded favorably; however, the two perianal fistulas required surgical resolution. Conclusions: Proctitis, ulcers and fistulas are nonspecific manifestations; the clinical and endoscopic findings per se are not sufficient to define the etiology; only a meticulous anamnesis allows us to presume an STI as a causative agent. The typification allows to define the biovar, a fundamental data to adapt the treatment, stop chain of transmission and provides local epidemiological data. As a result of this investigation, the Ministry of Health of the Argentina issued an alert about the presence of LGV in our country. Type of study: Observational, cross-sectional, analytical, multicenter study.

Candida albicans delays HIV-1 replication in macrophages.

Macrophages are one of the most important HIV-1 target cells. Unlike CD4(+) T cells, macrophages are resistant to the cytophatic effect of HIV-1. They are able to produce and harbor the virus for long periods acting as a viral reservoir. Candida albicans (CA) is a commensal fungus that colonizes the portals of HIV-1 entry, such as the vagina and the rectum, and becomes an aggressive pathogen in AIDS patients. In this study, we analyzed the ability of CA to modulate the course of HIV-1 infection in human monocyte-derived macrophages. We found that CA abrogated HIV-1 replication in macrophages when it was evaluated 7 days after virus inoculation. A similar inhibitory effect was observed in monocyte-derived dendritic cells. The analysis of the mechanisms responsible for the inhibition of HIV-1 production in macrophages revealed that CA efficiently sequesters HIV-1 particles avoiding its infectivity. Moreover, by acting on macrophages themselves, CA diminishes their permissibility to HIV-1 infection by reducing the expression of CD4, enhancing the production of the CCR5-interacting chemokines CCL3/MIP-1α, CCL4/MIP-1ß, and CCL5/RANTES, and stimulating the production of interferon-α and the restriction factors APOBEC3G, APOBEC3F, and tetherin. Interestingly, abrogation of HIV-1 replication was overcome when the infection of macrophages was evaluated 2-3 weeks after virus inoculation. However, this reactivation of HIV-1 infection could be silenced by CA when added periodically to HIV-1-challenged macrophages. The induction of a silent HIV-1 infection in macrophages at the periphery, where cells are continuously confronted with CA, might help HIV-1 to evade the immune response and to promote resistance to antiretroviral therapy.

The role of semen in sexual transmission of HIV: beyond a carrier for virus particles.

Unprotected sexual intercourse between discordant couples is by far the most frequent mode of HIV-1 (human immunodeficiency virus type 1) transmission being semen the main vector for HIV-1 dissemination worldwide. Semen is usually considered merely as a vehicle for HIV-1 transmission. In this review we discuss recent observations suggesting that beyond being a carrier for virus particles semen markedly influences the early events involved in sexual transmission of HIV through the mucosal barriers.

Epithelial cells activate plasmacytoid dendritic cells improving their anti-HIV activity.

Plasmacytoid dendritic cells (pDCs) play a major role in anti-viral immunity by virtue of their ability to produce high amounts of type I interferons (IFNs) and a variety of inflammatory cytokines and chemokines in response to viral infections. Since recent studies have established that pDCs accumulate at the site of virus entry in the mucosa, here we analyzed whether epithelial cells were able to modulate the function of pDCs. We found that the epithelial cell lines HT-29 and Caco-2, as well as a primary culture of human renal tubular epithelial cells (HRTEC), induced the phenotypic maturation of pDCs stimulating the production of inflammatory cytokines. By contrast, epithelial cells did not induce any change in the phenotype of conventional or myeloid DCs (cDCs) while significantly stimulated the production of the anti-inflammatory cytokine IL-10. Activation of pDCs by epithelial cells was prevented by Bafilomycin A1, an inhibitor of endosomal acidification as well as by the addition of RNase to the culture medium, suggesting the participation of endosomal TLRs. Interestingly, the cross-talk between both cell populations was shown to be associated to an increased expression of TLR7 and TLR9 by pDCs and the production of LL37 by epithelial cells, an antimicrobial peptide able to bind and transport extracellular nucleic acids into the endosomal compartments. Interestingly, epithelium-activated pDCs impaired the establishment of a productive HIV infection in two susceptible target cells through the stimulation of the production of type I IFNs, highlighting the anti-viral efficiency of this novel activation pathway.

Spermatozoa capture HIV-1 through heparan sulfate and efficiently transmit the virus to dendritic cells.

Semen is the main vector for HIV-1 dissemination worldwide. It contains three major sources of infectious virus: free virions, infected leukocytes, and spermatozoa-associated virions. We focused on the interaction of HIV-1 with human spermatozoa and dendritic cells (DCs). We report that heparan sulfate is expressed in spermatozoa and plays an important role in the capture of HIV-1. Spermatozoa-attached virus is efficiently transmitted to DCs, macrophages, and T cells. Interaction of spermatozoa with DCs not only leads to the transmission of HIV-1 and the internalization of the spermatozoa but also results in the phenotypic maturation of DCs and the production of IL-10 but not IL-12p70. At low values of extracellular pH (approximately 6.5 pH units), similar to those found in the vaginal mucosa after sexual intercourse, the binding of HIV-1 to the spermatozoa and the consequent transmission of HIV-1 to DCs were strongly enhanced. Our observations support the notion that far from being a passive carrier, spermatozoa acting in concert with DCs might affect the early course of sexual transmission of HIV-1 infection.

Dental beliefs in HIV+ patients with different oral health care needs

The aim of this work was to assess the score variation of scales 1 and 2 of the DCBS (Dental Coping Beliefs Scale) of beliefs on oral health regarding oral health needs, clinical progression of the viral infection, medical care needs, age and gender in HIV+ patients. The DCBS was randomly administered to 102 HIV+ patients at the "Juan A. Fernandez Hospital", Buenos Aires, Argentina. For each of the 29 items, patients indicated their responses on a five point scale ranging from "strongly disagree" to "strongly agree". Oral health needs were assessed through the CCITN (Community Caries Index of Treatment Need) and the CPITN (Community Periodontal Index of Treatment Need). Data on CD4 cell count, pharyngeal-esophageal candidiasis, tuberculosis, pneumonia and hospitalization because of HIV-related opportunistic diseases were recorded. A linear regression model was built in which the number of items reporting wrong dental beliefs was the dependent variable and the remaining variables were independent. Altogether 65.7% were male (36.0 ± 0.87 y.o.) and 34.3% were female (36.11 ± 1.21 y.o.) patients. The eight independent variables were significant for the model (F(8,93) = 93.20, p < 0.05; R = 0.80). The estimated parameters were all positive except for CD4 cell counts. The results demonstrate that the DCBS was useful to identify HIV+ patients as a caries and periodontal disease risk group because of their wrong dental beliefs and suggests the need of dental education interventions.

El propósito de este trabajo fue evaluar la variación del puntaje registrado para las subescalas 1 y 2 de la escala de creencias relativas a la salud bucal (DCBS) en relación a la necesidad de tratamiento odontológico, la progresión clínica de la infección viral, la necesidad de tratamiento medico, la edad y el genero de pacientes VIH+. El cuestionario correspondiente a la DCBS se administro aleatoriamente a 102 pacientes VIH+ concurrentes al Hospital Juan A. Fernandez, Buenos Aires, Argentina. Para cada una de las 29 proposiciones de las subescalas 1 y 2 de la DCBS los pacientes indicaron su parecer en una escala tipo Likert de 5 grados que iban desde “completamente en desacuerdo” hasta “completamente de acuerdo”. La necesidad de tratamiento odontológico se determino a través del Índice de Necesidad de Tratamiento de Caries de la Comunidad (INTCC) y del Índice de Necesidad de Tratamiento Periodontal de la Comunidad (INTPC). De la historia clínica medica de cada paciente se recabaron datos correspondientes al recuento de linfocitos T CD4, episodios de candidiasis faringoesofagica, tuberculosis, neumonía y hospitalización a raíz de enfermedades oportunistas afines a la infección por el VIH. Se construyo un modelo de regresión lineal tomando como variable dependiente el numero de proposiciones que reflejaban creencias erróneas sobre salud bucal mientras que las restantes variables en estudio se tomaron como independientes. El 65.7% de los pacientes en estudio correspondió a pacientes de genero masculino (36.0 ± 0.87 anos de edad) y el 34.3% restante a pacientes de genero femenino (36.11 ± 1.21 anos de edad). Las ocho variables independientes resultaron significativas para el modelo lineal (F(8,93) = 93.20, p < 0.05; R = 0.80). Los parámetros estimados para el modelo resultaron positivos excepto para el recuento de linfocitos T CD4. Los resultados indican que la DCBS resulta un instrumento útil para identificar a los pacientes VIH+ como un grupo de riesgo de caries y enfermedad periodontal dadas las creencias erróneas sobre salud bucal que poseen y sugieren la necesidad de intervenciones educativas de salud bucal en estos pacientes.

Nuevos conceptos en la transmisión sexual del HIV / New advances on sexual transmission of HIV

La transmisión sexual es la vía más importante de diseminación de la infección por HIV-1. Para lograr transmitirse por esta vía, el virus debe atravesar la barrera epitelial y alcanzar a las células blanco de la infección en el subepitelio: los linfocitos T CD4, los macrófagos y las células dendríticas. Los mecanismos subyacentes a la transmisión no son aún comprendidos con claridad. En los últimos años se ha resaltado la importancia de la interacción entre el HIV y las células dendríticas durante la transmisión y en la diseminación inicial del virus en la mucosa. El HIV, mediante complejos mecanismos, utiliza a las células dendríticas tanto como para favorecer su diseminación, como también para impedir la apropiada activación de la respuesta inmune adaptativa. Recientes hallazgos demuestran que durante la transmisión sexual, diferentes componentes del semen son capaces de modular esta interacción entre las células dendríticas y el HIV.(AU)

Unprotected sexual intercourse between discordant couples is by far the most common mode of human immunodeficiency virus type 1 (HIV-1) transmission. After deposition of HIV-1 on the recipient mucosa, infectious virus must cross the mucosal epithelium and interact with T CD4 lymphocytes, macrophages, and dendritic cells (DCs), which are the initial targets of infection. The mechanisms through which HIV-1 cross the mucosal epithelium and gain access to target cells are still not well characterized. The capacity of HIV-1 to hijack DCs appears to be crucial for viral transmission and early HIV-1 pathogenesis. HIV-1 subverts DC function favouring local dissemination of the virus and also interfering with the development of adaptive immune response. Recent findings show that semen modulates the interaction between dendritic cells and HIV during sexual transmission.(AU)

Nuevos conceptos en la transmisión sexual del HIV / New advances on sexual transmission of HIV

La transmisión sexual es la vía más importante de diseminación de la infección por HIV-1. Para lograr transmitirse por esta vía, el virus debe atravesar la barrera epitelial y alcanzar a las células blanco de la infección en el subepitelio: los linfocitos T CD4, los macrófagos y las células dendríticas. Los mecanismos subyacentes a la transmisión no son aún comprendidos con claridad. En los últimos años se ha resaltado la importancia de la interacción entre el HIV y las células dendríticas durante la transmisión y en la diseminación inicial del virus en la mucosa. El HIV, mediante complejos mecanismos, utiliza a las células dendríticas tanto como para favorecer su diseminación, como también para impedir la apropiada activación de la respuesta inmune adaptativa. Recientes hallazgos demuestran que durante la transmisión sexual, diferentes componentes del semen son capaces de modular esta interacción entre las células dendríticas y el HIV.

Unprotected sexual intercourse between discordant couples is by far the most common mode of human immunodeficiency virus type 1 (HIV-1) transmission. After deposition of HIV-1 on the recipient mucosa, infectious virus must cross the mucosal epithelium and interact with T CD4 lymphocytes, macrophages, and dendritic cells (DCs), which are the initial targets of infection. The mechanisms through which HIV-1 cross the mucosal epithelium and gain access to target cells are still not well characterized. The capacity of HIV-1 to hijack DCs appears to be crucial for viral transmission and early HIV-1 pathogenesis. HIV-1 subverts DC function favouring local dissemination of the virus and also interfering with the development of adaptive immune response. Recent findings show that semen modulates the interaction between dendritic cells and HIV during sexual transmission.