TBC laríngea: una localización poco común de la tuberculosis / Laryngeal tuberculosis: an unusual location for tuberculosis

Según datos de la OMS, la tuberculosis es una de las diez primeras causas de muerte en el mundo y es la primera causa de muerte por un agente infeccioso único. La incidencia de la tuberculosis ha disminuido por término medio un 1,5% anual desde el año 2000 sin embargo el impacto de la pandemia por el SARS-CoV-2 pudiera retardar el diagnóstico y tratamiento de nuevos casos de TB. Se presenta el caso de un paciente masculino de 26 años de edad quien consulta por presentar fiebre de predominio vespertino, pérdida de peso y disfonía de 6 meses de evolución. Los BK y cultivos de esputo seriados resultaron negativos. Es referido al Servicio de Otorrinolaringología y Cirugía Facial del Hospital Universitario Dr. Luis Gómez López donde se realiza una nasofibrolaringoscopía evidenciándose epiglotis con superficie de aspecto irregular que se extiende hasta aritenoides y zona interaritenoidea y bandas ventriculares edematizadas que no permiten visualizar repliegues vocales. Se realiza microcirugía laríngea para toma de biopsia reportando el estudio histopatológico proliferación de vasos neoformados, espacios intervasculares ocupados por macrófagos y linfocitos, presencia de múltiples lesiones nodulares formadas por macrófagos epiteloides rodeados por un halo de linfocitos y numerosas células gigantes de Langerhans. Se realiza el diagnóstico de tuberculosis laríngea y se inicia tratamiento antituberculoso(AU)

According to the WHO, tuberculosis represents one of the top ten causes of death worldwide and is the number one cause of death from a single infectious agent. The incidence of tuberculosis has decreased an average of 1.5% annually since the year 2000, however the impact of the SARS-CoV-2 pandemic could delay the diagnosis and treatment of new cases of TB. We report the case of a 26-year-old male who consulted for fever, weight loss and dysphonia with a duration of 6 months. BK and sputum cultures were negative for M. tuberculosis. The patient is referred to the Otorhinolaryngology and Facial Surgery Clinic of the Dr. Luis Gomez Lopez University Hospital where a nasofibrolaryngoscopy is performed showing an epiglottis with an irregular surface that extends to the arytenoids and interarytenoid zone and edematous ventricular bands that do not allow visualization of vocal folds. Laryngeal microsurgery is performed to obtain a biopsy sample. Histopathology reveals proliferation of newly formed vessels, intervascular spaces occupied by macrophages and lymphocytes, presence of multiple nodular lesions formed by epithelloid macrophages surrounded by a halo of lymphocytes and numerous giant Langerhans cells. Diagnosis of laryngeal tuberculosis is made and antituberculous treatment is initiated(AU)

Unique and overlapping gene expression patterns driven by IL-4 and IL-13 in the mouse lung.

BACKGROUND: Allergic asthma results from inappropriate T(H)2-mediated inflammation. Both IL-4 and IL-13 contribute to asthma pathogenesis, but IL-4 predominantly drives T(H)2 induction, whereas IL-13 is necessary and sufficient for allergen-induced airway hyperresponsiveness and goblet cell hyperplasia. Although these 2 cytokines share signaling components, the molecular mechanisms by which they mediate different phases of the allergic asthmatic response remain elusive. OBJECTIVE: We sought to clarify the role or roles of IL-4 and IL-13 in asthma-pathogenesis. METHODS: We used DNA Affymetrix microarrays to profile pulmonary gene expression in BALB/c mice inoculated intratracheally with ragweed pollen, house dust mite, IL-4, IL-13, or both cytokines. IL-13 dependence was confirmed by comparing pulmonary gene expression in house dust mite-inoculated wild-type and IL-13 knockout mice. RESULTS: A signature gene expression profile consisting of 23 genes was commonly induced by means of inoculation with house dust mite, ragweed pollen, or IL-4 plus IL-13. Although rIL-4 and rIL-13 treatment induced an overlapping set of genes, IL-4 uniquely induced 21 genes, half of which were interferon response genes and half of which were genes important in immunoregulation. IL-13 uniquely induced 8 genes, most of which encode proteins produced by epithelial cells. CONCLUSIONS: IL-4 and IL-13 together account for most allergen-induced pulmonary genes. Selective IL-4 induction of IFN-gamma response genes and other genes that might negatively regulate allergic inflammation could partially explain the greater importance of IL-13 in the effector phase of allergic airway disease.

Primer reporte de infección natural por Nocardia cyriacigeorgica en ratones BALB/c / First report of a natural infection by Nocardia cyriacigeorgica in BALB/c mice

Las bacterias del género Nocardia son actinomicetos aerobios cuyo hábitat es el suelo y la materia orgánica en descomposición. La infección natural por especies de este género ha sido reportada en humanos y animales, sin embargo, la infección natural en ratones no ha sido descrita. En este estudio se demuestra por primera vez el aislamiento de la especie recientemente descrita, Nocardia cyriacigeorgica, en pulmones de ratones Balb/c. El estudio microbiológico de las muestras de pulmón reportó la presencia de filamentos grampositivos ramificados fragmentados en forma cocobacilares. Los estudios de PCR demostraron que la especie aislada fue N. cyriacigeorgica. Se evidencia en este trabajo que N. cyriacigeorgica es potencialmente patógena en ratones Balb/c.

Bacteria belonging to the Nocardia genus are aerobic actinomycetae whose habitat is the ground and decomposing organic material. Natural infection by species belonging to this genus has been reported in humans and animals; nevertheless, natural infection in mice has not been described until now. This study demonstrates for the first time the isolation of a recently described species, Nocardia cyriacigeorgica, rom the lungs of Balb/c mice. The microbiological study of the lung samples reported the presence of branched Gram positive filaments with a cocobacillar shape. PCR studies demonstrated that the species isolated was N. cyriacigeorgica. This study demonstrates that N. cyriacigeorgica is potentially pathogenic for Balb/c mice.

Suppressive effect of IL-4 on IL-13-induced genes in mouse lung.

Although IL-4 signals through two receptors, IL-4R alpha/common gamma-chain (gamma(c)) and IL-4R alpha/IL-13R alpha1, and only the latter is also activated by IL-13, IL-13 contributes more than IL-4 to goblet cell hyperplasia and airway hyperresponsiveness in murine asthma. To determine whether unique gene induction by IL-13 might contribute to its greater proasthmatic effects, mice were inoculated intratracheally with IL-4 or IL-13, and pulmonary gene induction was compared by gene microarray and real-time PCR. Only the collagen alpha2 type VI (Ca2T6) gene and three small proline-rich protein (SPRR) genes were reproducibly induced > 4-fold more by IL-13 than by IL-4. Preferential IL-13 gene induction was not attributable to B cells, T cells, or differences in cytokine potency. IL-4 signaling through IL-4R alpha/gamma(c) suppresses Ca2T6 and SPRR gene expression in normal mice and induces these genes in RAG2/gamma(c)-deficient mice. Although IL-4, but not IL-13, induces IL-12 and IFN-gamma, which suppress many effects of IL-4, IL-12 suppresses only the Ca2T6 gene, and IL-4-induced IFN-gamma production does not suppress the Ca2T6 or SPRR genes. Thus, IL-4 induces genes in addition to IL-12 that suppress STAT6-mediated SPRR gene induction. These results provide a potential explanation for the dominant role of IL-13 in induction of goblet cell hyperplasia and airway hyperresponsiveness in asthma.

Amb a 1-linked CpG oligodeoxynucleotides reverse established airway hyperresponsiveness in a murine model of asthma.

BACKGROUND: Recently, it has been demonstrated that immunostimulatory DNA sequences (ISS) containing CpG motifs prevent the development of allergic airway responses in murine models of disease. However, few studies have addressed the issue of whether these agents will reverse established Tm(H)2-driven allergic airway responses. OBJECTIVE: The aim of this study was to determine whether intradermal delivery of an immunogenic protein of ragweed pollen linked to an immunostimulatory DNA sequence could reverse an established allergic response in the mouse lung. METHODS: Mice sensitized and challenged with ragweed pollen extract were treated intradermally twice at 1-week intervals with an ISS chemically linked to Amb a 1 (Amb a 1-ISS). One week after the Amb a 1-ISS treatment, mice were rechallenged intratracheally with ragweed extract, and airway responses were assessed. RESULTS: Amb a 1-ISS treatment of ragweed-sensitized and ragweed-challenged mice significantly reversed allergen-induced airway hyperresponsiveness and suppressed the total number of eosinophils in bronchoalveolar lavage fluid. The inhibitory effect of Amb a 1-ISS was associated with a marked increase in IFN-gamma levels by Amb a 1-stimulated splenocytes and a shift in the antibody profile from a T(H)2-directed IgG1 response to a T(H)1-directed IgG2a response. Interestingly, the inhibitory effect of Amb a 1-ISS on allergen-driven airway hyperresponsiveness was independent of suppression of T(H)2 cytokine production. CONCLUSION: These results demonstrate that intradermal delivery of allergen-specific DNA conjugates can reverse established allergic responses in the murine lung, supporting their potential use in the treatment of human asthma.