Transmission of malaria from donors to solid organ transplant recipients: A case report and literature review.

Malaria is a febrile and potentially fatal infection. It is typically transmitted to humans through the bite of Anopheles mosquitoes and less frequently can be contracted through blood transfusions, sharing contaminated needles and syringes, mother-to-child transmission, or after solid organ transplantation. Posttransplant malaria has rarely been reported in the literature, even in endemic areas. We report the cases of three solid organ recipients in which Plasmodium vivax infection was documented during postsurgical evaluation 30 days after transplant surgery. The diagnosis of donor-derived malaria was confirmed in all patients by demonstrating Plasmodium in a peripheral blood smear and by polymerase chain reaction (PCR). All recipients had symptoms. The liver transplant recipient had myalgia, arthralgia, and thrombocytopenia; the kidney transplant recipient developed acute renal failure; and the heart transplant recipient had fever, cephalalgia, and tonic-clonic seizures. Pre-transplant screening of donors and recipients from endemic regions may not be sufficient to safely rule out persistent malaria. In Colombia, according to legislation, no mandatory testing is required for the diagnosis of malaria in organ donors in nonendemic areas. Therefore, donor screening by questionnaire is the only tool for preventing transplant-borne malaria. The migratory trend from Venezuela to Colombia has increased the number of imported cases of malaria, and the infection may be present in endemic and nonendemic regions. Although donor evaluation is not standardized in current guidelines, we suggest that donors be tested for malaria with a peripheral blood smear, detection of specific IgG antibodies against Plasmodium, and techniques such as PCR, if possible.

B cell depletion therapies in autoimmune disease: advances and mechanistic insights.

In the past 15 years, B cells have been rediscovered to be not merely bystanders but rather active participants in autoimmune aetiology. This has been fuelled in part by the clinical success of B cell depletion therapies (BCDTs). Originally conceived as a method of eliminating cancerous B cells, BCDTs such as those targeting CD20, CD19 and BAFF are now used to treat autoimmune diseases, including systemic lupus erythematosus and multiple sclerosis. The use of BCDTs in autoimmune disease has led to some surprises. For example, although antibody-secreting plasma cells are thought to have a negative pathogenic role in autoimmune disease, BCDT, even when it controls the disease, has limited impact on these cells and on antibody levels. In this Review, we update our understanding of B cell biology, review the results of clinical trials using BCDT in autoimmune indications, discuss hypotheses for the mechanism of action of BCDT and speculate on evolving strategies for targeting B cells beyond depletion.

Gut microbiota-specific IgA+ B cells traffic to the CNS in active multiple sclerosis.

Changes in gut microbiota composition and a diverse role of B cells have recently been implicated in multiple sclerosis (MS), a central nervous system (CNS) autoimmune disease. Immunoglobulin A (IgA) is a key regulator at the mucosal interface. However, whether gut microbiota shape IgA responses and what role IgA+ cells have in neuroinflammation are unknown. Here, we identify IgA-bound taxa in MS and show that IgA-producing cells specific for MS-associated taxa traffic to the inflamed CNS, resulting in a strong, compartmentalized IgA enrichment in active MS and other neuroinflammatory diseases. Unlike previously characterized polyreactive anti-commensal IgA responses, CNS IgA cross-reacts with surface structures on specific bacterial strains but not with brain tissue. These findings establish gut microbiota-specific IgA+ cells as a systemic mediator in MS and suggest a critical role of mucosal B cells during active neuroinflammation with broad implications for IgA as an informative biomarker and IgA-producing cells as an immune subset to harness for therapeutic interventions.

Early-life programming of mesenteric lymph node stromal cell identity by the lymphotoxin pathway regulates adult mucosal immunity.

Redundant mechanisms support immunoglobulin A (IgA) responses to intestinal antigens. These include multiple priming sites [mesenteric lymph nodes (MLNs), Peyer's patches, and isolated lymphoid follicles] and various cytokines that promote class switch to IgA, even in the absence of T cells. Despite these backup mechanisms, vaccination against enteric pathogens such as rotavirus has limited success in some populations. Genetic and environmental signals experienced during early life are known to influence mucosal immunity, yet the mechanisms for how these exposures operate remain unclear. Here, we used rotavirus infection to follow antigen-specific IgA responses through time and in different gut compartments. Using genetic and pharmacological approaches, we tested the role of the lymphotoxin (LT) pathway-known to support IgA responses-at different developmental stages. We found that LT-ß receptor (LTßR) signaling in early life programs intestinal IgA responses in adulthood by affecting antibody class switch recombination to IgA and subsequent generation of IgA antibody-secreting cells within an intact MLN. In addition, early-life LTßR signaling dictates the phenotype and function of MLN stromal cells to support IgA responses in the adult. Collectively, our studies uncover new mechanistic insights into how early-life LTßR signaling affects mucosal immune responses during adulthood.

Sobrecarga y calidad de vida de vida del cuidador de un paciente con esquizofrenia / Overload and quality of life of the caregiver of a patient with schizophrenia

El propósito del estudio fue evaluar el grado de sobrecarga y la calidad de vida relacionada con la salud de los cuidadores primarios informales de pacientes con esquizofrenia. Se propuso estudio de tipo descriptivo observacional. Fueron encuestados 131 cuidadores con la escala de Sobrecarga de Zarit, y el Test SF-36. Se analizó la asociación entre variables; además del nivel de significación. En los resultados se identificó el 94,8% de los cuidadores se encuentran entre los grupos de edades de 19 a 68 años, el género que más aporta al cuidado es femenino con el 63%, se evidencia que el 63% de los cuidadores se encuentran en algún grado de sobrecarga (32% ligera) (31% intensa), la calidad de vida del cuidador en la función física obtuvo las puntuaciones más altas, junto con la dimensión de salud general, seguidas por la vitalidad y la salud mental con las puntuaciones más bajas. Podemos concluir el ejercicio del cuidado de un paciente con esquizofrenia representa un cambio en la calidad de vida del cuidador y este se encuentra directamente relacionado con el grado de sobrecarga asociado al cuidado.

The purpose of the study was to assess the degree of overload and quality of life related to the health of informal primary caregivers of patients with schizophrenia. An observational descriptive study was proposed. A total of 131 caregivers were surveyed with the Zarit overload scale and the SF-36 test. The association between variables was analyzed; in addition to the level of significance. In the results we identified 94.8% of the caregivers are among the age group of 19 to 68 years, the gender that contributes most to care is female with 63%, it is evident that 63% of the caregivers are in some degree of overload (32% light) (31% intense), the quality of life of the caregiver in physical function obtained the highest scores, along with the general health dimension, followed by vitality and mental health with the scores lower. We conclude the exercise of caring for a patient with schizophrenia represents a change in the quality of life of the caregiver and this is directly related to the degree of overload associated with care.

Molecular identification of unusual Mycetoma agents isolated from patients in Venezuela.

Mycetoma is a chronic granulomatous, subcutaneous disease endemic in tropical and subtropical countries. It is currently a health problem in rural areas of Africa, Asia and South America. Nine cases of mycetoma were analysed in a retrospective study. All isolates were identified by morphological features. The level of species identification was reached by molecular tools. Definitive identification of fungi was performed using sequence analysis of the ITS of the ribosomal DNA region and the ribosomal large-subunit D1/D2. Identification of actinomycetes was accomplished by the 16S rRNA gene sequence. Six unusual clinical isolates were identified: Aspergillus ustus, Cyphellophora oxyspora, Exophiala oligosperma, Madurella pseudomycetomatis, Nocardia farcinica and Nocardia wallacei. The prevalence of mycetoma in Venezuela remains unknown. This study represents the first report in the literature of mycetoma caused by unusual pathogens identified by molecular techniques.

Hematopoietic LTßR deficiency results in skewed T cell cytokine profiles during a mucosal viral infection.

The lymphotoxin signaling pathway plays an important role in the homeostasis and function of peripheral and mucosal dendritic cells, and dendritic cell-intrinsic lymphotoxin ß receptor expression is required for optimal responses to opportunistic intestinal bacteria. However, it is unknown whether dendritic cell-intrinsic lymphotoxin ß receptor signaling is required for responses to intestinal viral infections. We explored this question by orally administrating murine rotavirus to chimeric mice that lack lymphotoxin ß receptor signaling in the myeloid compartment but retain lymphoid tissues. We found that although clearance of rotavirus was unimpaired in the lymphotoxin ß receptor(-/-) → wild-type chimeric mice compared with wild-type → wild-type chimeric mice, IFN-γ-producing CD8(+) and CD4(+) T cells were significantly increased in the small intestinal lamina propria of lymphotoxin ß receptor(-/-) → wild-type chimeric mice. In contrast, IL-17-producing CD4(+) T cells were reduced in lymphotoxin ß receptor(-/-) → wild-type chimeric mice in the steady state, and this reduction persisted after rotavirus inoculation. In spite of this altered cytokine profile in the small intestinal lamina propria of lymphotoxin ß receptor(-/-) → wild-type chimeric mice, the local production of rotavirus-specific IgA was unperturbed. Collectively, our results demonstrate that lymphotoxin ß receptor signaling in radio-sensitive myeloid cells regulates the balance of IFN-γ and IL-17 cytokine production within the small intestinal lamina propria; however, these perturbations do not affect mucosal antiviral IgA responses.

Disseminated bronchiectasis in an adult with common variable immunodeficiency.

Primary immunodeficiencies (PID) are traditionally considered childhood diseases; however, adults account for 35% of all patients with PID. Antibody deficiencies, especially Common Variable Immunodeficiency (CVID), which have their peak incidence in adulthood, require a high suspicion index. Even though the estimated frequency of CVID is not high (1:25,000), high rates of under diagnosis and under reporting are very likely. The delay in diagnosis increases the morbidity and mortality; therefore, adult physicians should be able to suspect, identify and initiate management of individuals with PID. Here we report the case of a 37 year-old man presenting to the emergency room with dyspnea, fever and cough; he developed respiratory failure requiring mechanical ventilation. He complained of recurring pneumonia associated with widespread bronchiectasis since he was 18 years old. Serum immunoglobulins quantification showed severe hypogammaglobulinemia (total IgG <140 mg/dL; total IgA, 2.9 mg/dL; and total IgM <5 mg/dL). Treatment with Human Intravenous Immunoglobulin (IVIG) 10% was started, and with antibiotic treatment for severe pneumonia (during 14 days) was also prescribed. His clinical evolution has been favorable after one year follow-up. Common Variable Immunodeficiency (CVID) diagnosis was made.

Las inmunodeficiencias primarias (IDP) son patologías que tradicionalmente se consideran de la niñez sin embargo los adultos representan el 35% del total de pacientes con IDP. Las deficiencias de anticuerpos, en especial la Inmunodeficiencia Común Variable (IDCV) tienen su pico de incidencia en la edad adulta, requiere un alto índice de sospecha y si bien su frecuencia estimada no es alta (1:25,000), es muy posible que el subregistro y subdiagnóstico si lo sean. El retraso en el diagnóstico aumenta la morbi-mortalidad razón por la cual los médicos de adultos deben estar en capacidad de sospechar, identificar e iniciar el manejo de las personas con IPD. Presentamos el caso de un hombre de 37 años de edad atendido en la sala de urgencias con disnea, fiebre y tos, desarrolla falla respiratoria requiriendo ventilación mecánica. Refería neumonías a repetición desde los 18 años de edad asociadas con bronquiectasias generalizadas. La cuantificación de inmunoglobulinas séricas evidenció hipogammaglobulinemia severa (IgG total <140 mg/dL, IgA total 2.9 mg/dL, IgM total <5 mg/dL), se inició inmunoglobulina humana endovenosa (IGIV) al 10%, y recibió tratamiento antibiótico por 14 días para neumonía severa, su evolución clínica ha sido favorable hasta ahora (un año de seguimiento), se estableció el diagnostico de Inmunodeficiencia Común Variable (IDCV).

Disseminated bronchiectasis in an adult with common variable immunodeficiency / Bronquiectasias diseminada en un adulto con inmunodeficiencia común variable

Primary immunodeficiencies (PID) are traditionally considered childhood diseases; however, adults account for 35% of all patients with PID. Antibody deficiencies, especially Common Variable Immunodeficiency (CVID), which have their peak incidence in adulthood, require a high suspicion index. Even though the estimated frequency of CVID is not high (1:25,000), high rates of under diagnosis and under reporting are very likely. The delay in diagnosis increases the morbidity and mortality; therefore, adult physicians should be able to suspect, identify and initiate management of individuals with PID. Here we report the case of a 37 year-old man presenting to the emergency room with dyspnea, fever and cough; he developed respiratory failure requiring mechanical ventilation. He complained of recurring pneumonia associated with widespread bronchiectasis since he was 18 years old. Serum immunoglobulins quantification showed severe hypogammaglobulinemia (total IgG <140 mg/dL; total IgA, 2.9 mg/dL; and total IgM <5 mg/dL). Treatment with Human Intravenous Immunoglobulin (IVIG) 10% was started, and with antibiotic treatment for severe pneumonia (during 14 days) was also prescribed. His clinical evolution has been favorable after one year follow-up. Common Variable Immunodeficiency (CVID) diagnosis was made.

Las inmunodeficiencias primarias (IDP) son patologías que tradicionalmente se consideran de la niñez sin embargo los adultos representan el 35% del total de pacientes con IDP. Las deficiencias de anticuerpos, en especial la Inmunodeficiencia Común Variable (IDCV) tienen su pico de incidencia en la edad adulta, requiere un alto índice de sospecha y si bien su frecuencia estimada no es alta (1:25,000), es muy posible que el subregistro y subdiagnóstico si lo sean. El retraso en el diagnóstico aumenta la morbi-mortalidad razón por la cual los médicos de adultos deben estar en capacidad de sospechar, identificar e iniciar el manejo de las personas con IPD. Presentamos el caso de un hombre de 37 años de edad atendido en la sala de urgencias con disnea, fiebre y tos, desarrolla falla respiratoria requiriendo ventilación mecánica. Refería neumonías a repetición desde los 18 años de edad asociadas con bronquiectasias generalizadas. La cuantificación de inmunoglobulinas séricas evidenció hipogammaglobulinemia severa (IgG total <140 mg/dL, IgA total 2.9 mg/dL, IgM total <5 mg/dL), se inició inmunoglobulina humana endovenosa (IGIV) al 10%, y recibió tratamiento antibiótico por 14 dias para neumonía severa, su evolución clínica ha sido favorable hasta ahora (un año de seguimiento), se estableció el diagnostico de Inmunodeficiencia Común Variable (IDCV).

Re-thinking the functions of IgA(+) plasma cells.

The intestinal mucosa harbors the largest population of antibody (Ab)-secreting plasma cells (PC) in the human body, producing daily several grams of immunoglobulin A (IgA). IgA has many functions, serving as a first-line barrier that protects the mucosal epithelium from pathogens, toxins and food antigens (Ag), shaping the intestinal microbiota, and regulating host-commensal homeostasis. Signals induced by commensal colonization are central for regulating IgA induction, maintenance, positioning and function and the number of IgA(+) PC is dramatically reduced in neonates and germ-free (GF) animals. Recent evidence demonstrates that the innate immune effector molecules tumor necrosis factor α (TNFα) and inducible nitric oxide synthase (iNOS) are required for IgA(+) PC homeostasis during the steady state and infection. Moreover, new functions ascribed to PC independent of Ab secretion continue to emerge, suggesting that PC, including IgA(+) PC, should be re-examined in the context of inflammation and infection. Here, we outline mechanisms of IgA(+) PC generation and survival, reviewing their functions in health and disease.

Simultaneous assessment of rotavirus-specific memory B cells and serological memory after B cell depletion therapy with rituximab.

The mechanisms that contribute to the maintenance of serological memory are still unclear. Rotavirus (RV) memory B cells (mBc) are enriched in IgM(+) and CD27- subpopulations, which are associated with autoimmune diseases pathogenesis. In patients with autoimmune diseases treated with Rituximab (RTX), some autoantibodies (auto-Abs) decrease after treatment, but other auto-Abs and pathogen-specific IgG Abs remain unchanged. Thus, maintenance of autoimmune and pathogen-specific serological memory may depend on the type of antigen and/or Ab isotype evaluated. Antigen-specific mBc and antigen-specific Abs of different isotypes have not been simultaneously assessed in patients after RTX treatment. To study the relationship between mBc subpopulations and serological memory we characterized total, RV- and tetanus toxoid (TT)-specific mBc by flow cytometry in patients with autoimmune diseases before and after treatment with RTX. We also measured total, RV- and TT-Abs, and some auto-Abs by kinetic nephelometry, ELISA, and EliA tests, respectively. Minor differences were observed between the relative frequencies of RV-mBc in healthy controls and patients with autoimmune disease. After RTX treatment, naïve Bc and total, RV- and TT-specific mBc [IgM(+), switched (IgA(+)/IgG(+)), IgM(+) only, IgD(+) only, and CD27- (IgA(+)/IgG(+)/IgM(+))] were significantly diminished. An important decrease in total plasma IgM and minor decreases in total IgG and IgA levels were also observed. IgM rheumatoid factor, IgG anti-CCP, and IgG anti-dsDNA were significantly diminished. In contrast, RV-IgA, RV-IgG and RV-IgG1, and TT-IgG titers remained stable. In conclusion, in patients with autoimmunity, serological memory against RV and TT seem to be maintained by long-lived plasma cells, unaffected by RTX, and an important proportion of total IgM and serological memory against some auto-antigens seem to be maintained by short-lived plasma cells, dependent on mBc precursors depleted by RTX.

A TNF-α-CCL20-CCR6 axis regulates Nod1-induced B cell responses.

Innate immune responses provoke the accumulation of leukocytes at sites of inflammation. In addition to monocytes and granulocytes, B cells also participate in antimicrobial innate immune responses; however, the mechanisms for accumulation of B cells to sites of inflammation are not well understood. To study B cell accumulation following systemic inflammation, we used a model synthetic ligand that stimulates a specific pattern recognition molecule, nucleotide-binding oligomerization domain-containing protein 1 (Nod1). Upon exposure to Nod1 agonists, both B cells and neutrophils rapidly accumulate within the spleen, and dendritic cells migrate into the periarterial lymphoid sheath. Nod1 stimulation led to a marked increase in several chemokines within the spleen, including CXCL13, CCL2, and CCL20. Whereas the lymphotoxin pathway was critical for the induction of the B cell chemoattractant CXCL13 in response to Nod1 agonists, B cell accumulation within the spleen following Nod1-induced systemic inflammation was independent of the lymphotoxin pathway. In contrast, a CCR6/CCL20 chemokine loop instructed rapid increase of B cells in the spleen in response to systemic administration of Nod1 agonists in a TNF-α-dependent manner. Moreover, CCR6 was required to regulate Nod1-mediated B cell responses. These results reveal a novel mechanism of B cells during inflammation and shed light on how B cells participate in innate immune responses to microbial stimulation.

Conductas sexuales asociadas a preeclampsia severa en pacientes del Servicio de Obstetricia del Hospital de Apoyo María Auxiliadora / Pre-eclampsia associated sexual behaviors in hospitalized patients with severe pre-eclampsia at the Obstetrics Department of Hospital de Apoyo María Auxiliadora

Objetivos: determinar las conductas sexuales asociadas a preeclampsia severa en pacientes hospitalizadas. Material y Métodos: se realizó una encuesta a 41 pacientes con preeclampsia severa para obtener datos con respecto a edad de primera gestación y de primera relación sexual (RS), número de parejas sexuales, hijos con parejas diferentes, frecuencia de coito, duración de RS previa al embarazo, exposición a semen y tiempo de cohabitación con la pareja. Resultados: Se encontró una edad promedio de 19 años para la primera gestación y de 17 para la primera RS, el 63% refirió más de 1 pareja sexual. El 15% presentaba relaciones sexuales durante menos de 6 meses antes del embarazo y el 90% y 22% presentaba exposición a semen según método anticonceptivo usado y sexo oral respectivamente. Conclusiones: las conductas sexuales asociadas con preeclampsia severa, estuvieron presentes en nuestra población con variable correlación a los hallazgos de otros estudios.

Objectives: to determine the presence of pre-eclampsia-associated sexual behaviors in our environment.Material and Methods: Forty-one patients were surveyed in order to obtain the results for age of first pregnancy and first sexual intercourse, number of sexual partners, children with different partners, sexual intercourse frequency, duration of sexual relationship, semen exposure and partner cohabitation period. Results: a mean age of 19 years-old was found for the first pregnancy and of 17 for the first sexual intercourse, 63% had more than 1 total sexual partners. Sexual relationship shorter than 6 months was present in 15% or the surveyed and semen exposure according to contraceptive methods and oral sex was of 90% and 22% respectively. Conclusions: sexual behaviors associated with pre-eclampsia were found in our population with a variable co-relation to the findings of other studies.

AID and caspase 8 shape the germinal center response through apoptosis.

Germinal centers (GCs) are clusters of activated B cells that form in secondary lymphoid organs during a T-dependent immune response. B cells enter GCs and become rapidly proliferating centroblasts that express the enzyme activation-induced deaminase (AID) to undergo somatic hypermutation and class-switch recombination. Centroblasts then mature into centrocytes to undergo clonal selection. Within the GC, the highest affinity B cell clones are selected to mature into memory or plasma cells while lower affinity clones undergo apoptosis. We reported previously that murine Aicda(-/-) GC B cells have enhanced viability and accumulate in GCs. We now show that murine Aicda(-/-) GC B cells accumulate as centrocytes and inefficiently generate plasma cells. The reduced rate of plasma cell formation was not due to an absence of AID-induced DNA lesions. In addition, we show that the deletion of caspase 8 specifically in murine GC-B cells results in larger GCs and a delay in affinity maturation, demonstrating the importance of apoptosis in GC homeostasis and clonal selection.

Colecistectomía laparoscópica difícil, estrategias de manejo / Difficult laparoscopic cholecystectomy, management strategies

La colecistectomía laparoscópica es uno de los procedimientos quirúrgicos practicados más frecuentemente por el cirujano general y en un importante número de casos se efectúa en pacientes mayores con gran inflamación vesicular, lo que pone a prueba los conocimientos y habilidades del cirujano. Es perfectamente posible reconocer, antes del acto quirúrgico, en cuáles pacientes este resultará difícil en mayor o menor grado, para así diseñar estrategias de manejo intraoperatorio que nos permitan resolver favorablemente estos casos. En este artículo, el cual se presenta acompañado de videos de casos clínicos publicados en la página electrónica de la Asociación Colombiana de Cirugía (http://www.ascolcirugia.org), se pretende mostrar cuáles son las opciones de manejo en aquellos pacientes cuyas colecistectomías son muy difíciles por el grado de inflamación o por las enfermedades subyacentes y que constituyen alternativas de manejo viables para la colecistectomía laparoscópica clásica o para evitar la conversión a cirugía abierta; aunque también, se llama fuertemente la atención sobre la necesidad de una conversión temprana y oportuna antes de tener complicaciones o alteraciones iatrogénicas de la vía biliar u otro órgano vecino.

Laparoscopic cholecystectomy is one of the most commonly performed procedures by the general surgeon and an important number of cases occur in elderly patients with major inflammation of the gallbladder, a condition that challenges the knowledge and ability of the surgeon. It is perfectible possible to recognize, prior to surgery, which patients will present major or minor difficulties so as to design intraoperative strategies in order to favorably resolve such situations. This article is complemented wit uploaded YouTube videos in the web page of the Asociación Colombiana de Cirugía, http://www.ascolcirugia.org. It intends to show the different management options in those patients with very difficult cholecystectomies because of the degree of inflammation or the underlying pathology that constitute viable alternatives to the classic laparoscopic cholecystectomy or to avoid conversion open surgery; however, it also strongly calls attention to the need of early and timely conversion so as to avoid complications or iatrogenic lesion of the bile duct or neighbor organs.

Human myeloid dendritic cells treated with supernatants of rotavirus infected Caco-2 cells induce a poor Th1 response.

We have previously shown that human myeloid dendritic cells treated with purified rotavirus induce an allogenic Th1 response. To determine if rotavirus in the context of an intestinal microenvironment modulates the function of dendritic cells, we treated these cells with supernatants from non-infected or infected Caco-2 cells and studied their capacity to promote Th1 or Th2 responses. Dendritic cells treated with supernatants from rotavirus-infected Caco-2 cells promoted a significantly lower Th1 response, in comparison with those treated with purified rotavirus. We wanted to establish if TGF-ß1, induced, or TSLP, not induced, during rotavirus infection, could mediate this effect. Neutralization of TGF-ß but not TSLP in the supernatant prior to treatment of dendritic cells increased their capacity to promote a Th1 response. The results suggest that the TGF-ß1 induced by rotavirus could be an immune evasion mechanism, and may partially explain the poor rotavirus-specific T cell response we have previously evidenced.

Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut.

The largest mucosal surface in the body is in the gastrointestinal tract, a location that is heavily colonized by microbes that are normally harmless. A key mechanism required for maintaining a homeostatic balance between this microbial burden and the lymphocytes that densely populate the gastrointestinal tract is the production and transepithelial transport of poly-reactive IgA (ref. 1). Within the mucosal tissues, B cells respond to cytokines, sometimes in the absence of T-cell help, undergo class switch recombination of their immunoglobulin receptor to IgA, and differentiate to become plasma cells. However, IgA-secreting plasma cells probably have additional attributes that are needed for coping with the tremendous bacterial load in the gastrointestinal tract. Here we report that mouse IgA(+) plasma cells also produce the antimicrobial mediators tumour-necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS), and express many molecules that are commonly associated with monocyte/granulocytic cell types. The development of iNOS-producing IgA(+) plasma cells can be recapitulated in vitro in the presence of gut stroma, and the acquisition of this multifunctional phenotype in vivo and in vitro relies on microbial co-stimulation. Deletion of TNF-α and iNOS in B-lineage cells resulted in a reduction in IgA production, altered diversification of the gut microbiota and poor clearance of a gut-tropic pathogen. These findings reveal a novel adaptation to maintaining homeostasis in the gut, and extend the repertoire of protective responses exhibited by some B-lineage cells.

Estacionalidad y tendencia de las atenciones médicas por enfermedades diarreicas agudas en la provincia de Ciego de Ávila / Seasonality and trend of medical care for acute diarrheal diseases in Ciego de Avila

Se realizó una investigación ecológica de serie cronológica (1999-2010) de las enfermedades diarreicas agudas en la provincia de Ciego de Ávila para evaluar la estacionalidad y tendencia de las atenciones médicas por esta enfermedad y pronosticar su frecuencia para el año 2011. El universo lo conformó el total de atenciones médicas por enfermedades diarreicas agudas en la provincia durante los años referidos. La información mensual y anual se obtuvo de los registros del Departamento Provincial de Estadística. Las atenciones médicas por esta enfermedad mostraron una tendencia descendente hasta el año 2004, para posteriormente mantenerse estacionaria hasta el año 2006, a partir del cual se observan incrementos en los años 2007, 2009 y 2010. El pronóstico para el año 2011 fue de 65.9 x 103 habitantes (IC 95 por ciento 72,3-59,5). Los métodos gráficos utilizados para el tratamiento de la serie temporal, evidenciaron estacionalidad con un incremento significativo de las atenciones médicas en el segundo trimestre del año. El mes de junio es el de mayor frecuencia de atenciones médicas, los meses de julio y junio fueron los de mayor variabilidad y el más consistente resultó el mes de noviembre. La serie resultó rítmica con incrementos estacionales cada 4 meses

An ecological research of time series of acute diarrheal diseases was carried out in Ciego de Avila to assess the seasonality and trend of medical care for this disease and predict its frequency to 2011. The universe cosisted of the total medical care for acute diarrheal diseases during the years in question. Monthly and annual records were obtained from the Provincial Department of Statistics.Medical care for acute diarrheal diseases showed a downward trend until 2004, then remained steady until 2006, after which there were increases in 2007, 2009 and 2010. The forecast for 2011 was 65.9 x 103 inhabitants (IC 95 percent 72,3-59,5). Graphical methods used to treat the time series, showed seasonality with significant increase of medical care in the second trimester. June is the month most often in medical care, June and July were the most variability and the most consistent was November. The series was rhythmic with seasonal increases every four months

Membrane vesicles released by intestinal epithelial cells infected with rotavirus inhibit T-cell function.

Rotavirus (RV) predominantly replicates in intestinal epithelial cells (IEC), and "danger signals" released by these cells may modulate viral immunity. We have recently shown that human model IEC (Caco-2 cells) infected with rhesus-RV release a non-inflammatory group of immunomodulators that includes heat shock proteins (HSPs) and TGF-ß1. Here we show that both proteins are released in part in association with membrane vesicles (MV) obtained from filtrated Caco-2 supernatants concentrated by ultracentrifugation. These MV express markers of exosomes (CD63 and others), but not of the endoplasmic reticulum (ER) or nuclei. Larger quantities of proteins associated with MV were released by RV-infected cells than by non-infected cells. VP6 co-immunoprecipitated with CD63 present in these MV, and VP6 co-localized with CD63 in RV-infected cells, suggesting that this viral protein is associated with the MV, and that this association occurs intracellularly. CD63 present in MV preparations from stool samples from 36 children with gastroenteritis due or not due to RV were analyzed. VP6 co-immunoprecipitated with CD63 in 3/8 stool samples from RV-infected children, suggesting that these MV are released by RV-infected cells in vivo. Moreover, fractions that contained MV from RV-infected cells induced death and inhibited proliferation of CD4(+) T cells to a greater extent than fractions from non-infected cells. These effects were in part due to TGF-ß, because they were reversed by treatment of the T cells with the TGF-ß-receptor inhibitor ALK5i. MV from RV-infected and non-infected cells were heterogeneous, with morphologies and typical flotation densities described for exosomes (between 1.10 and 1.18 g/mL), and denser vesicles (>1.24 g/mL). Both types of MV from RV-infected cells were more efficient at inhibiting T-cell function than were those from non-infected cells. We propose that RV infection of IEC releases MV that modulate viral immunity.