Role of inmunoregulatory cells during porcine reproductive and respiratory syndrome

El Síndrome Reproductivo y Respiratorio Porcino (PRRS) es una de las enfermedades que más pérdidas económicas ocasiona al sector porcino mundial. Su agente causal, el virus del PRRS (PRRSV), comprende 2 genotipos, dentro de los cuales se encuentran cepas de diversa virulencia. El PRRSV es capaz de infectar las células presentadoras de antígeno (APCs), las cuales desempeñan un papel crucial en la activación de los linfocitos T, por tanto, el estudio de la interacción del PRRSV y las APCs mejorará el actual conocimiento que se tiene sobre la patogenia de esta enfermedad. Para conseguir este objetivo se realizaron estudios in vivo e in vitro analizando la expresión de diversos marcadores de diferenciación y activación, la proliferación de linfocitos T, así como, ensayos de susceptibilidad a la infección por el virus. Durante el transcurso de la infección con el PRRSV en el estudio in vivo se observó una disminución en el número de células que expresaban el Complejo Mayor de Histocompatibilidad de clase II (MHC-II) en los animales inoculados desde el primer día de estudio (3 dpi) hasta el final del experimento. Los resultados de nuestro segundo estudio mostraron que las células dendríticas derivadas de monocitos (MoDCs) eran permisivas para el PRRSV y que, las células infectadas por el virus expresaban mayor cantidad de las moléculas MHC-II y CD80/86, las cuales disminuían a las 48 horas post-inoculación. Por otro lado, la infección de MoDCs con el PRRSV no indujo proliferación de linfocitos T ni proliferación y efecto supresor de linfocitos T reguladores (Tregs). En los ensayos de susceptibilidad, llevados a cabo en células dendríticas derivadas de médula ósea, se observó que el PRRSV podría inducir la muerte de las mismas principalmente asociada a fenómenos de necrosis pero no de apoptosis. Con todo ello, los resultados derivados de nuestros estudios in vivo e in vitro señalan que el PRRSV podría inducir la muerte de APCs con elevada capacidad de presentación antigénica y, con ello, provocar un fallo en la instauración de la respuesta inmune adaptativa específica frente al virus. Asimismo, en nuestro estudio no se observó un efecto en la proliferación de los Tregs ni de otras subpoblaciones de linfocitos T

Las células presentadoras de antígeno y su papel en el síndrome reproductivo y respiratorio porcino

Las células presentadoras de antígeno son aquellas células encargadas de capturar, procesar y presentar antígenos con la finalidad de lograr una respuesta inmune efectiva por parte del organismo. Su papel, como centinelas, es crucial durante el transcurso de diversas enfermedades infecciosas. El estudio de estas células tras la infección con el virus del Síndrome Reproductivo y Respiratorio Porcino nos da información para abordar nuevas estrategias de control frente a esta enfermedad.Antigen presenting cells are able to capture, process and present antigens in order to develop an effective immune response. The role of these cells during infectious diseases is crucial to control the disease. Thus, the study of these cells after the infection with Porcine Reproductive and Respiratory Syndrome Virus gives us useful information on how to control this disease

The jigsaw of PRRSV virulence

Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of the, probably, most economically important disease for the pig industry worldwide. This disease, characterised by producing reproductive failure in sows and respiratory problems in growing pigs, appeared in the late 1980s in the United States and Canada. Since its appearance, strains capable of producing higher mortality rates as well as greater severity in clinical signs and lesions than classical strains have been identified. However, since the first reports of these “virulent” PRRSV outbreaks, no homogeneity and consensus in their description have been established. Moreover, to the authors’ knowledge, there is no published information related to the criteria that a PRRSV strain should fulfil to be considered as a “virulent” strain. In this review, we revise the terminology used and gather the information related to the main characteristics and differences in clinical signs, lesions, viral replication and tropism as well as immunological parameters between virulent and classical PRRSV strains and propose a first approximation to the criteria to define a virulent PRRSV strain

Bases de la respuesta inflamatoria en la forma respiratoria del PRRS

El Síndrome Reproductivo y Respiratorio Porcino (PRRS) es una enfermedad de distribución mundial que causa graves pérdidas económicas al sector porcino. Este virus no sólo es importante como agente causal del PRRS sino también por su participación en el desarrollo del Complejo Respiratorio Porcino. Su interacción con las defensas pulmonares, la alteración de la respuesta inmune y su persistencia en los órganos linfoides conlleva a que los cerdos tengan dificultades para luchar contra la enfermedad.Porcine Reproductive and Respiratory Syndrome (PRRS) is considered as the most economically important disease of the modern swine industry. The importance of this virus lies in not only being the causative agent of PRRSV, but also due to its implication in the onset of the Porcine Respiratory Disease Complex. The interaction of the virus with pulmonary defenses, the impairment of the immune response as well as the viral persistence in lymphoid organs make overcoming the disease diffi cult to infected pigs

Activation of T-bet, FOXP3, and EOMES in Target Organs From Piglets Infected With the Virulent PRRSV-1 Lena Strain

Transcription factors (TFs) modulate genes involved in cell-type-specific proliferative and migratory properties, metabolic features, and effector functions. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogen agents in the porcine industry; however, TFs have been poorly studied during the course of this disease. Therefore, we aimed to evaluate the expressions of the TFs T-bet, GATA3, FOXP3, and Eomesodermin (EOMES) in target organs (the lung, tracheobronchial lymph node, and thymus) and those of different effector cytokines (IFNG, TNFA, and IL10) and the Fas ligand (FASL) during the early phase of infection with PRRSV-1 strains of different virulence. Target organs from mock-, virulent Lena-, and low virulent 3249-infected animals humanely euthanized at 1, 3, 6, 8, and 13 days post-infection (dpi) were collected to analyze the PRRSV viral load, histopathological lesions, and relative quantification through reverse transcription quantitative PCR (RT-qPCR) of the TFs and cytokines. Animals belonging to both infected groups, but mainly those infected with the virulent Lena strain, showed upregulation of the TFs T-bet, EOMES, and FOXP3, together with an increase of the cytokine IFN-g in target organs at the end of the study (approximately 2 weeks post-infection). These results are suggestive of a stronger polarization to Th1 cells and regulatory T cells (Tregs), but also CD4+ cytotoxic T lymphocytes (CTLs), effector CD8+ T cells, and gdT cells in virulent PRRSV-1-infected animals; however, their biological functionality should be the object of further studies

Activation of pro- and anti-inflammatory responses in lung tissue injury during the acute phase of PRRSV-1 infection with the virulent strain Lena

Porcine reproductive and respiratory syndrome virus (PRRSV) plays a key role in porcine respiratory disease complex modulating the host immune response and favouring secondary bacterial infections. Pulmonary alveolar macrophages (PAMs) are the main cells supporting PRRSV replication, with CD163 as the essential receptor for viral infection. Although interstitial pneumonia is by far the representative lung lesion, suppurative bronchopneumonia is described for PRRSV virulent strains. This research explores the role of several immune markers potentially involved in the regulation of the inflammatory response and sensitisation of lung to secondary bacterial infections by PRRSV-1 strains of different virulence. Conventional pigs were intranasally inoculated with the virulent subtype 3 Lena strain or the low virulent subtype 1 3249 strain and euthanised at 1, 3, 6 and 8 dpi. Lena-infected pigs exhibited more severe clinical signs, macroscopic lung score and viraemia associated with an increase of IL-6 and IFN-γ in sera compared to 3249-infected pigs. Extensive areas of lung consolidation corresponding with suppurative bronchopneumonia were observed in Lena-infected pigs. Lung viral load and PRRSV-N-protein+ cells were always higher in Lena-infected animals. PRRSV-N-protein+ cells were linked to a marked drop of CD163+ macrophages. The number of CD14+ and iNOS+ cells gradually increased along PRRSV-1 infection, being more evident in Lena-infected pigs. The frequency of CD200R1+ and FoxP3+ cells peaked late in both PRRSV-1 strains, with a strong correlation between CD200R1+ cells and lung injury in Lena-infected pigs. These results highlight the role of molecules involved in the earlier and higher extent of lung lesions in piglets infected with the virulent Lena strain, pointing out the activation of routes potentially involved in the restraint of the local inflammatory response.info:eu-repo/semantics/acceptedVersio

Ruxolitinib in refractory acute and chronic graft-versus-host disease : a multicenter survey study

Graft-versus-host disease is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. First-line treatment is based on the use of high doses of corticosteroids. Unfortunately, second-line treatment for both acute and chronic graft-versus-host disease, remains a challenge. Ruxolitinib has been shown as an effective and safe treatment option for these patients. Seventy-nine patients received ruxolitinib and were evaluated in this retrospective and multicenter study. Twenty-three patients received ruxolitinib for refractory acute graft-versus-host disease after a median of 3 (range 1-5) previous lines of therapy. Overall response rate was 69.5% (16/23) which was obtained after a median of 2 weeks of treatment, and 21.7% (5/23) reached complete remission. Fifty-six patients were evaluated for refractory chronic graft-versus-host disease. The median number of previous lines of therapy was 3 (range 1-10). Overall response rate was 57.1% (32/56) with 3.5% (2/56) obtaining complete remission after a median of 4 weeks. Tapering of corticosteroids was possible in both acute (17/23, 73%) and chronic graft-versus-host disease (32/56, 57.1%) groups. Overall survival was 47% (CI: 23-67%) at 6 months for patients with aGVHD (62 vs 28% in responders vs non-responders) and 81% (CI: 63-89%) at 1 year for patients with cGVHD (83 vs 76% in responders vs non-responders). Ruxolitinib in the real life setting is an effective and safe treatment option for GVHD, with an ORR of 69.5% and 57.1% for refractory acute and chronic graft-versus-host disease, respectively, in heavily pretreated patients

Distribution and outcomes of a phenotype-based approach to guide COPD management: Results from the CHAIN cohort

Rationale: The Spanish guideline for COPD (GesEPOC) recommends COPD treatment according to four clinical phenotypes: non-exacerbator phenotype with either chronic bronchitis or emphysema (NE), asthma-COPD overlap syndrome (ACOS), frequent exacerbator phenotype with emphysema (FEE) or frequent exacerbator phenotype with chronic bronchitis (FECB). However, little is known on the distribution and outcomes of the four suggested phenotypes. Objective: We aimed to determine the distribution of these COPD phenotypes, and their relation with one-year clinical outcomes. Methods: We followed a cohort of well-characterized patients with COPD up to one-year. Baseline characteristics, health status (CAT), BODE index, rate of exacerbations and mortality up to one year of follow-up were compared between the four phenotypes. Results: Overall, 831 stable COPD patients were evaluated. They were distributed as NE, 550 (66.2%); ACOS, 125 (15.0%); FEE, 38 (4.6%); and FECB, 99 (11.9%); additionally 19 (2.3%) COPD patients with frequent exacerbations did not fulfill the criteria for neither FEE nor FECB. At baseline, there were significant differences in symptoms, FEV1 and BODE index (all p<0.05). The FECB phenotype had the highest CAT score (17.1±8.2, p<0.05 compared to the other phenotypes). Frequent exacerbator groups (FEE and FECB) were receiving more pharmacological treatment at baseline, and also experienced more exacerbations the year after (all p<0.05) with no differences in one-year mortality. Most of NE (93%) and half of exacerbators were stable after one year. Conclusions: There is an uneven distribution of COPD phenotypes in stable COPD patients, with significant differences in demographics, patient-centered outcomes and health care resources use