RESUMEN
OBJECTIVE: Microscopic colitis is a not uncommon chronic inflammatory disease of the colon, characterized by watery, non-bloody diarrhea, which is often forgotten and misdiagnosed. CASE PRESENTATION: In this paper, we present a puzzling case of relapsing chronic diarrhea triggered by non-steroidal anti-inflammatory drug (NSAID) abuse, smoking, inappropriate antibiotic use, and secondary Clostridium Difficilis infection. Several tests were performed during hospitalization, all of which were negative apart from fecal calprotectin (> 6,000 mg/kg, normal values < 50 mg/kg) and a positive Clostridium Difficilis toxin test. Since Vancomycin treatment did not bring about the expected response, colonoscopy was performed, which led to diagnosis, targeted therapy, and clinical resolution. Targeted therapy with budesonide and probiotics was initiated leading to resolution of the diarrhea. CONCLUSIONS: This case study shows how actual diagnosis may be delayed not only due to having to perform differential diagnosis with chronic inflammatory diseases, but also because certainty can only come from histological evidence, which takes time to obtain, especially when the disease's multifactorial nature is considered (smoking, NSAID abuse, oral proton pump inhibitors, inappropriate antibiotic use, and Clostridium difficilis infection).
Asunto(s)
Colitis Microscópica , Humanos , Colitis Microscópica/diagnóstico , Colitis Microscópica/tratamiento farmacológico , Colitis Microscópica/patología , Diarrea/diagnóstico , Diarrea/tratamiento farmacológico , Diarrea/etiología , Antiinflamatorios no Esteroideos/uso terapéutico , Antibacterianos/uso terapéuticoRESUMEN
OBJECTIVE: Several mRNA vaccines have been developed to tackle the global pandemic. Despite their remarkable clinical efficacy, they are not devoid of severe short- and long-term adverse events. CASE PRESENTATION: In this paper, we describe a rare delayed adverse event (arterial and venous renal thrombosis with myocardial injury) in an otherwise healthy adult female, which occurred three months after she received a booster shot of Pfizer COVID-19 vaccine. The patient was successfully treated for subacute renal ischemia with intra-arterial urokinase, and her myocardial injury was diagnosed with imaging (contrast-enhanced thoracic CT and cardiac magnetic resonance) and percutaneous coronary intervention. Deferred post-vaccine myocarditis was diagnosed and resolved with steroid therapy. CONCLUSIONS: In this paper, we report a useful clinical case for the pharmacovigilance database. Although scientific evidence confirms that the benefits of vaccination far outweigh the risk of adverse events, we would like to point out how important watchful observation is in the medium and long term, especially when the subject belongs to a specific risk category.
Asunto(s)
COVID-19 , Vacunas , Adulto , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Bases de Datos Factuales , Femenino , Humanos , Vacunación/efectos adversosRESUMEN
BACKGROUND: Paracentesis-induced circulatory dysfunction (PICD) is a "silent killer syndrome" occurring after large volume paracenteses (LVPs). We here report an unusual case of PICD induced by right heart failure recognized and managed successfully. CASE PRESENTATION: A 60-year-old woman was admitted to our Emergency Department for worsening dyspnea and hypoxia. Her medical history enclosed a chronic heart failure with reduced ejection fraction and post-stroke dysarthria associated to right hemiplegia. Clinical and laboratory examination defined a severe right-heart failure unresponsive to high-dose diuretic therapy. Diagnostic and therapeutic paracentesis was thus performed determining, initially, a progressive normalization of the abdominal volume, followed, subsequently, by a severe hypotension associated with an acute kidney injury (AKI) combined with severe hyponatremia associated with a normal cardiac output. In the hypothesis of a PICD, abdominal drainage and diuretic therapy were interrupted, reninemia sampling was performed, resulting in diagnostic, and treatment with albumin and norepinephrine was started. The latter was tapered and then replaced with Midodrine that conferred the possibility to reach clinical and laboratory stability, allowing relocation in a cardiological rehabilitation. PICD represents an independent predictor of mortality. Midodrine's prophylactic use in PICD has been suggested as a cheaper alternative to albumin, as it appears to improve renal perfusion and reduce ascites with better clinical handling, as demonstrated in our patient. CONCLUSIONS: Our clinical case wants to show how not all PICDs are secondary to hepatic dysfunctions with Midodrine playing a possible therapeutic role by counteracting the pathophysiological mechanism in a rapid and non-invasive way, representing a valid therapeutic option in adjunction to albumin.
Asunto(s)
Insuficiencia Cardíaca , Midodrina , Choque , Humanos , Femenino , Persona de Mediana Edad , Midodrina/uso terapéutico , Paracentesis/efectos adversos , Resultado del Tratamiento , Cirrosis Hepática/complicaciones , Albúminas/uso terapéutico , Ascitis/etiología , Ascitis/terapia , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/etiología , Diuréticos/uso terapéuticoRESUMEN
Although 80% of HIV infections occur through mucosal routes and vaccine strategies need to be designed for inducing protective immune responses at the site of the viral entry, it has proven to be very challenging to measure these responses. A 2-day workshop was convened by Division of AIDS, National Institutes of Health on June 15-16, 2009 to address the challenges encountered in the evaluation of mucosal T cell immune responses. The goal of the workshop was to obtain recommendations/consensus for developing standardized protocols for the assessment of mucosal immunity. This report summarizes the areas of consensus and recommendations that should assist in developing standardized methodologies for the evaluation of mucosal immune responses.
Asunto(s)
Inmunidad Celular/inmunología , Inmunidad Mucosa/inmunología , Femenino , Infecciones por VIH/inmunología , Humanos , Masculino , Membrana Mucosa/inmunología , National Institutes of Health (U.S.) , Estados UnidosRESUMEN
Type 2 cytokines regulate fibrotic liver pathology in mice infected with Schistosoma mansoni. Switching the immune response to a type 1-dominant reaction has proven highly effective at reducing the pathologic response. Activation of NOS-2 is critical, because type 1-deviated/NO synthase 2 (NOS-2)-deficient mice completely fail to control their response. Here, we demonstrate the differential regulation of NOS-2 and arginase type 1 (Arg-1) by type 1/type 2 cytokines in vivo and for the first time show a critical role for arginase in the pathogenesis of schistosomiasis. Using cytokine-deficient mice and two granuloma models, we show that induction of Arg-1 is type 2 cytokine dependent. Schistosome eggs induce Arg-1, while Mycobacterium avium-infected mice develop a dominant NOS-2 response. IFN-gamma suppresses Arg-1 activity, because type 1 polarized IL-4/IL-10-deficient, IL-4/IL-13-deficient, and egg/IL-12-sensitized animals fail to up-regulate Arg-1 following egg exposure. Notably, granuloma size decreases in these type-1-deviated/Arg-1-unresponsive mice, suggesting an important regulatory role for Arg-1 in schistosome egg-induced pathology. To test this hypothesis, we administered difluoromethylornithine to block ornithine-aminodecarboxylase, which uses the product of arginine metabolism, L-ornithine, to generate polyamines. Strikingly, granuloma size and hepatic fibrosis increased in the ornithine-aminodecarboxylase-inhibited mice. Furthermore, we show that type 2 cytokine-stimulated macrophages produce proline under strict arginase control. Together, these data reveal an important regulatory role for the arginase biosynthetic pathway in the regulation of inflammation and demonstrate that differential activation of Arg-1/NOS-2 is a critical determinant in the pathogenesis of granuloma formation.
Asunto(s)
Arginasa/metabolismo , Arginina/metabolismo , Granuloma/inmunología , Granuloma/patología , Óxido Nítrico Sintasa/metabolismo , Células TH1/inmunología , Células Th2/inmunología , Animales , Arginasa/antagonistas & inhibidores , Arginasa/biosíntesis , Células Cultivadas , Modelos Animales de Enfermedad , Eflornitina/farmacología , Activación Enzimática/efectos de los fármacos , Activación Enzimática/genética , Activación Enzimática/inmunología , Inducción Enzimática/efectos de los fármacos , Inducción Enzimática/genética , Inducción Enzimática/inmunología , Inhibidores Enzimáticos/farmacología , Femenino , Granuloma/enzimología , Granuloma/prevención & control , Interleucina-12/fisiología , Hígado/enzimología , Cirrosis Hepática/enzimología , Cirrosis Hepática/patología , Enfermedades Pulmonares Parasitarias/enzimología , Enfermedades Pulmonares Parasitarias/genética , Enfermedades Pulmonares Parasitarias/inmunología , Enfermedades Pulmonares Parasitarias/patología , Activación de Macrófagos , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mycobacterium avium/inmunología , Óxido Nítrico Sintasa/biosíntesis , Óxido Nítrico Sintasa de Tipo II , Inhibidores de la Ornitina Descarboxilasa , Óvulo/inmunología , Prolina/biosíntesis , Esquistosomiasis mansoni/enzimología , Esquistosomiasis mansoni/genética , Esquistosomiasis mansoni/inmunología , Esquistosomiasis mansoni/patología , Células TH1/enzimología , Células Th2/enzimología , Tuberculosis/enzimología , Tuberculosis/genética , Tuberculosis/inmunología , Tuberculosis/patología , Regulación hacia Arriba/genética , Regulación hacia Arriba/inmunologíaRESUMEN
A human immunodeficiency virus (HIV) type 1-transgenic mouse line (166) that previously showed up-regulated expression of viral proteins and infectious particles after infection with pathogenic agents was tested as a model for screening the in vitro and in vivo efficacy of inhibitors of HIV-1 immune activation. Two types of interventions were assessed: use of either the immunosuppressive drug prednisolone or an HIV-1 envelope-targeted toxin (sCD4-PE40). Both agents inhibited lipopolysaccharide-induced p24 expression by splenocytes in vitro and, when administered to transgenic mice, suppressed the induction of plasma p24, as well as the ex vivo production of p24 and infectious virus stimulated by in vivo infection with Mycobacterium avium. Moreover, HIV-1 mRNA levels in the spleen were greatly reduced in mice treated with either agent. Because HIV-1 expression cannot be induced in T lymphocytes from line 166 mice, this model may be of particular advantage for testing interventions that target virus production by non-T cell virus reservoirs.
Asunto(s)
Fármacos Anti-VIH/farmacología , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Provirus/efectos de los fármacos , Animales , Fármacos Anti-VIH/administración & dosificación , Antígenos CD4/administración & dosificación , Antígenos CD4/farmacología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Exotoxinas/administración & dosificación , Exotoxinas/farmacología , Glucocorticoides/administración & dosificación , Glucocorticoides/farmacología , Proteína p24 del Núcleo del VIH/sangre , Infecciones por VIH/sangre , Infecciones por VIH/microbiología , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Inmunotoxinas/administración & dosificación , Inmunotoxinas/farmacología , Lipopolisacáridos , Ratones , Ratones Transgénicos , Mycobacterium avium , Prednisolona/administración & dosificación , Prednisolona/farmacología , Provirus/metabolismo , ARN Mensajero/análisis , ARN Viral/genética , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacología , Bazo/efectos de los fármacos , Bazo/virologíaRESUMEN
To test the capacity of malaria parasites to trigger virus expression in vivo, human immunodeficiency virus (HIV) transgenic mice were infected with Plasmodium chabaudi chabaudi clone AS. Splenocytes recovered during peak parasitemia showed a dramatic elevation in viral p24 production that returned to baseline by day 15 and failed to rebound at recrudescence or after reinfection. The major sources of virus expression were antigen-presenting cells (APCs) rather than T lymphocytes. Nevertheless, T cells from infected mice stimulated with plasmodial antigen triggered 5-10-fold increases in p24 production from dendritic cells in vitro, which suggests that viral induction stems from interaction of malaria-specific T lymphocytes with HIV-expressing APCs. Indeed, depletion of CD4 T cells resulted in a 70% reduction in the p24 response stimulated by malaria in vivo. These findings demonstrate the ability of Plasmodium species to immunologically activate latently integrated HIV in vivo but suggest that this process may be restricted to acute infection.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/inmunología , VIH/fisiología , Malaria/inmunología , Malaria/virología , Plasmodium chabaudi , Replicación Viral , Animales , Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/virología , Células Dendríticas/inmunología , Células Dendríticas/virología , VIH/genética , Proteína p24 del Núcleo del VIH/sangre , Infecciones por VIH/complicaciones , Humanos , Activación de Linfocitos , Malaria/complicaciones , Ratones , Ratones Transgénicos , Parasitemia/inmunología , Parasitemia/virología , Bazo/inmunologíaRESUMEN
Because of their relative resistance to viral cytopathic effects, APC can provide an alternative reservoir for latently integrated HIV. We used an HIV-transgenic mouse model in which APC serve as the major source of inducible HIV expression to study mechanisms by which integrated virus can be activated in these cells. When admixed with transgenic APC, activated T lymphocytes provided a major contact-dependent stimulus for viral protein expression in vitro. Using blocking anti-CD154 mAb as well as CD154-deficient T cells, the HIV response induced by activated T lymphocytes was demonstrated to require CD40-CD154 interaction. The role of this pathway in the induction of HIV expression from APC in vivo was further studied in an experimental model involving infection of the HIV-transgenic mice with PLASMODIUM: chabaudi parasites. Enhanced viral production by dendritic cells and macrophages in infected mice was associated with up-regulated CD40 expression. More importantly, in vivo treatment with blocking anti-CD154 mAb markedly reduced viral expression in P. chabaudi-infected animals. Together, these findings indicate that immune activation of integrated HIV can be driven by the costimulatory interaction of activated T cells with APC. Because chronic T cell activation driven by coinfections as well as HIV-1 itself is a characteristic of HIV disease, this pathway may be important in sustaining viral expression from APC reservoirs.
Asunto(s)
Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/virología , Antígenos CD40/metabolismo , Ligando de CD40/metabolismo , VIH-1/genética , VIH-1/inmunología , Integración Viral/inmunología , Animales , Anticuerpos Bloqueadores/farmacología , Anticuerpos Monoclonales/farmacología , Antivirales/farmacología , Antígenos CD40/inmunología , Antígenos CD40/fisiología , Ligando de CD40/inmunología , Ligando de CD40/fisiología , Comunicación Celular/genética , Comunicación Celular/inmunología , Células Cultivadas , Técnicas de Cocultivo , Células Dendríticas/inmunología , Células Dendríticas/virología , Femenino , VIH-1/crecimiento & desarrollo , Activación de Linfocitos/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Modelos Inmunológicos , Plasmodium chabaudi/inmunología , Bazo/citología , Bazo/inmunología , Bazo/virología , Linfocitos T/inmunología , Linfocitos T/virología , Activación Viral/inmunología , Integración Viral/genéticaRESUMEN
CD40 ligation triggers IL-12 production by dendritic cells (DC) in vitro. Here, we demonstrate that CD40 cross-linking alone is not sufficient to induce IL-12 production by DC in vivo. Indeed, resting DC make neither the IL-12 p35 nor IL-12 p40 subunits and express only low levels of CD40. Nevertheless, after DC activation by microbial stimuli that primarily upregulate IL-12 p40 and augment CD40 expression, CD40 ligation induces a significant increase in IL-12 p35 and IL-12 p70 heterodimer production. Similarly, IL-12 p70 is produced during T cell activation in the presence but not in the absence of microbial stimuli. Thus, production of bioactive IL-12 by DC can be amplified by T cell-derived signals but must be initiated by innate signals.
Asunto(s)
Antígenos de Protozoos/administración & dosificación , Antígenos de Protozoos/inmunología , Antígenos CD40/fisiología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Interleucina-12/biosíntesis , Transducción de Señal/inmunología , Células 3T3 , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/fisiología , Animales , Anticuerpos Monoclonales/administración & dosificación , Antígenos CD40/biosíntesis , Antígenos CD40/inmunología , Células Cultivadas , Células Dendríticas/citología , Células Dendríticas/parasitología , Dimerización , Femenino , Inyecciones Intraperitoneales , Inyecciones Intravenosas , Interleucina-12/metabolismo , Interfase/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones SCID , Ratones Transgénicos , Linfocitos T/inmunología , Toxoplasma/inmunología , Regulación hacia Arriba/inmunologíaRESUMEN
A low molecular weight (LMW) antigen of Eimeria tenella, initially identified using a murine monoclonal antibody (mAb C(3)4F(1)) raised against E. tenella sporozoites, was partially characterized using enzymatic degradation. solvent extraction, and immunization into various inbred lines of mice. The LMW antigen could be isolated using Folch extraction (methanol/chloroform/ water) and the epitope recognized by mAb C(3)4F(1) was resistant to degradation by alpha-amylase, pronase, and proteinase K, but was sensitive to sodium m-periodate treatment or digestion using mixed glycosidases (from Turbo cornutus). These observations suggest that the antigenic epitope recognized by mAb C(3)4F(1) is carbohydrate-dependent and, based on our ability to isolate the LMW antigen by Folch extraction, the epitope probably resides on a polar glycolipid. The inability of sporozoite-immunized nude mice to elicit a serum antibody response to this molecule indicates that it acts as a T-dependent antigen. Furthermore, sporozoite-immunized male CBA/N mice (with an X-linked immunodeficiency) also failed to elicit a serum antibody response to this molecule, which is consistent with a carbohydrate antigenic epitope. We propose that this antigenic molecule be designated ET-GL1 to reflect its origin and probable structure (E. tenella glycolipid 1).
Asunto(s)
Antígenos de Protozoos/química , Eimeria tenella/inmunología , Glucolípidos/inmunología , Animales , Anticuerpos Antiprotozoarios , Ligamiento Genético , Síndromes de Inmunodeficiencia , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Peso Molecular , Cromosoma XRESUMEN
The activation of dendritic cells (DC) to produce interleukin 12 (IL-12) is thought to be a key step in the initiation of cell-mediated immunity to intracellular pathogens. Here we show that ligation of the C-C chemokine receptor (CCR) 5 can provide a major signal for the induction of IL-12 synthesis by the CD8 alpha+ subset of DC and that this pathway is important in establishing interferon gamma-dependent resistance to the protozoan parasite Toxoplasma gondii. These findings support the concept that the early induction of chemokines by invading pathogens is a critical step not only for the recruitment of DC but also for the determination of their subsequent immunologic function.
Asunto(s)
Antígenos CD8/inmunología , Células Dendríticas/inmunología , Interleucina-12/inmunología , Receptores CCR5/inmunología , Toxoplasma/inmunología , Toxoplasmosis/inmunología , Animales , Antígenos de Protozoos/inmunología , Inmunidad Celular , Ratones , Transducción de Señal/inmunologíaRESUMEN
Interleukin-12 plays a major role in immunity to intracellular pathogens by governing the development of IFNgamma-dependent host resistance. Nevertheless, unregulated IL-12 synthesis can lead to immunopathology, an outcome prevented by the concurrent expression of interleukin-10. Dendritic cells (DC) are an important source of the initial IL-12 stimulated by microbial agents. Here, we show that, following systemic triggering, DC can no longer be restimulated to produce IL-12 in vivo while continuing to respond in vitro. When infected with Toxoplasma gondii during this refractory state, mice mount impaired acute IFNgamma responses and, in the case of IL-10-deficient animals, are protected from cytokine-induced mortality. These findings demonstrate a previously unrecognized form of immunologic paralysis involving DC that can protect from infection-induced immunopathology.
Asunto(s)
Antígenos de Protozoos/inmunología , Células Dendríticas/inmunología , Interleucina-12/fisiología , Modelos Inmunológicos , Toxoplasma/inmunología , Toxoplasmosis Animal/inmunología , Animales , Antígenos de Protozoos/farmacología , Células Cultivadas , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Interacciones Huésped-Parásitos , Interferón gamma/biosíntesis , Interferón gamma/deficiencia , Interleucina-10/deficiencia , Interleucina-10/genética , Interleucina-12/biosíntesis , Interleucina-12/deficiencia , Interleucina-12/genética , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Noqueados , Bazo/inmunología , Toxoplasmosis Animal/complicaciones , Toxoplasmosis Animal/patologíaRESUMEN
Infection of HIV-1-transgenic mice with Mycobacterium avium, a common opportunistic pathogen in AIDS patients, was shown to result in increased tissue expression of viral specific transcripts. Moreover, by coculturing splenocytes from the transgenic animals with human T cells it was possible to demonstrate that the elevation in HIV-1 mRNA triggered by M. avium infection reflects increased production of infectious virions. Viral immune activation was also shown to correlate with a marked elevation of p24 in supernatants of ex vivo-cultured tissues and, more importantly, in systemic increases in the HIV-1 protein in plasma. Interestingly, these tissue and systemic p24 responses were found to be differentially regulated. Thus, while in vitro p24 production by cultured splenocytes increased concurrently with bacterial loads during the first 6 wk of infection, levels of the Ag in plasma actually decreased. In situ localization experiments together with FACS analysis of HIV-1-expressing splenocytes indicated that virus production is restricted largely to cells of the monocyte/macrophage lineage. Indeed, in vitro p24 expression by cells from noninfected transgenic mice was up-regulated by polyclonal stimulation of macrophages but not T cells. Together these results underscore the importance of the macrophage reservoir in persistent virus expression and establish a convenient and relevant animal model for studying the factors responsible for immune activation of HIV-1 induced by mycobacterial as well as other common coinfections encountered by AIDS patients.
Asunto(s)
VIH-1/genética , VIH-1/inmunología , Antígeno de Macrófago-1/biosíntesis , Mycobacterium avium/inmunología , Tuberculosis/inmunología , Tuberculosis/virología , Activación Viral/inmunología , Animales , Células Cultivadas , Productos del Gen gag/genética , Proteína p24 del Núcleo del VIH/sangre , VIH-1/crecimiento & desarrollo , Humanos , Macrófagos/inmunología , Macrófagos/virología , Ratones , Ratones Endogámicos , Ratones Transgénicos , Especificidad de Órganos/genética , ARN Mensajero/metabolismo , Bazo/citología , Bazo/virología , Toxoplasma/inmunología , Toxoplasmosis Animal/genética , Toxoplasmosis Animal/inmunología , Toxoplasmosis Animal/virología , Tuberculosis/genética , Tuberculosis/patología , Virión/crecimiento & desarrollo , Virión/patogenicidad , Activación Viral/genética , Replicación Viral/inmunologíaRESUMEN
Two distinct mechanisms seem to function in reducing oocyst output during Eimeria papillata infections in mice. For naive mice, immunity was afforded by a T-cell-independent gamma-interferon (IFN-gamma) response mediated by natural killer (NK) cells. On reinfection, resistance was associated with T-cells and, to a lesser extent, perforin. To determine if antigen presentation with major histocompatibility complex (MHC) molecules was required to control oocyst production by NK cells during primary infection or by T-cells during secondary infection, mutant mice that lacked H2-IAbeta(b) (Abeta(b)-/-) or beta2-microglobulin (beta2m-/-) were used. Since MHC molecules are required for the maturation of alphabeta T-cells, Abeta(b)-/- and beta2m-/- mutant mice are also deficient in functional alphabeta+CD4+ or alphabeta+CD8+ T-cells, respectively. As compared with wild-type control mice, oocyst output by mutant mice was not significantly affected during primary infection, suggesting that the ability of NK cells to control parasite replication is not dependent on the expression of MHC molecules. On reinfection, differences were observed for mutant mice as compared with controls. Abeta(b)-/- mice were found to be more susceptible than beta2m-/- mice, suggesting that the alphabeta+CD4+ T-cell subset plays a greater role in resistance to reinfection than does the alphabeta+CD8+ T-cell subset. The mechanism of resistance depends on the immune status of the host and requires the coordinated interaction of both alphabeta+ T-cell subsets for optimal parasite control during subsequent infections.
Asunto(s)
Coccidiosis/inmunología , Eimeria/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Animales , Presentación de Antígeno , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Coccidiosis/parasitología , Susceptibilidad a Enfermedades , Eimeria/crecimiento & desarrollo , Heces/parasitología , Inmunidad Innata , Células Asesinas Naturales/inmunología , Masculino , Ratones , Ratones Noqueados , Recuento de Huevos de Parásitos , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Factores de TiempoRESUMEN
BALB/c mice were infected with the intestinal intracellular parasite Eimeria papillata to characterize lymphocyte responses and cytokine profiles throughout primary and secondary infections. Lymphocytes from the mesenteric lymph node (MLN) and the gastrointestinal tract (GIT) of infected mice were phenotypically analyzed using flow cytometry and immunofluorescence microscopy, respectively. Lymphocytes isolated from the MLN during primary infections of BALB/c mice with E. papillata do not proliferate, compared to day 0 uninfected controls, when stimulated in vitro with conconavalin A and express TH2-type cytokines (interleukin [IL]-4 and IL-10) on day 3 PI followed by the release of TH1-type cytokines (IL-2 and interferon-gamma) during patency. In the small intestine, significantly more T cells and their subsets were observed during primary infection. During secondary infections, IL-2 was the only 1 of the 4 cytokines that was expressed earlier and at higher levels in the MLN when compared to primary infections. In the small intestine, significantly more alphabeta+ and CD8+ T lymphocytes were observed in mice during secondary infection. Oocyst antigens did not induce cellular proliferation at any time point during primary or secondary infections. We conclude that primary oral infection of BALB/c mice with E. papillata is associated with localized immunosuppression that may be mediated, in part, by early TH2-type cytokines. Immunity to secondary infection may be mediated by intestinal alphabeta+ CD8+ T lymphocytes through an IL-2-dependent mechanism.
Asunto(s)
Coccidiosis/inmunología , Citocinas/biosíntesis , Eimeria/inmunología , Parasitosis Intestinales/inmunología , Intestino Delgado/inmunología , Ganglios Linfáticos/inmunología , Animales , Modelos Animales de Enfermedad , Intestino Delgado/patología , Ganglios Linfáticos/patología , Activación de Linfocitos , Linfocitos/inmunología , Masculino , Mesenterio , Ratones , Ratones Endogámicos BALB CRESUMEN
Two laboratory strains from the eastern shore of Maryland 15 years ago and from an Ontario broiler house 23 years ago and three recent field strains of Eimeria maxima (isolated in Maryland, North Carolina and Florida) were examined for phenotypic and genotypic variation using protein profiles, random amplified polymorphic DNA-PCR analysis and DNA sequences obtained from the internal transcribed spacer regions of the rRNA genes. Staining profiles obtained by one-dimensional SDS-PAGE of sporozoite proteins were identical in all five strains. Using random amplified polymorphic DNA-PCR analysis with high %G-C content decamers as primers, we were able to confirm that the five strains are all E. maxima, but were unable to discern any relationships among them because of the limited number of shared polymorphisms identified. In contrast, cloning and sequencing of the internal transcribed spacer-1, 5.8S rDNA and internal transcribed spacer-2 regions of the rRNA genes provided sufficient sequence information to infer phylogenetic relationships among the strains. Almost all of the infraspecific variation was located in the internal transcribed spacer regions. Only two base changes were identified within the 5.8S rRNA gene. Evolutionary relationships among the strains inferred using parsimony analysis of the aligned internal transcribed spacer sequences were well supported, but the hypothesised relationships did not correlate well with the demonstrated immunological cross-reactivities of these strains.
Asunto(s)
Pollos/parasitología , Coccidiosis/veterinaria , Eimeria/clasificación , Variación Genética , Enfermedades de las Aves de Corral/parasitología , Animales , Coccidiosis/parasitología , Cartilla de ADN/química , ADN Protozoario/análisis , ADN Protozoario/química , ADN Ribosómico/análisis , ADN Ribosómico/química , Eimeria/genética , Eimeria/inmunología , Electroforesis en Gel de Poliacrilamida/veterinaria , Genotipo , América del Norte , Fenotipo , Filogenia , Reacción en Cadena de la Polimerasa/veterinaria , Polimorfismo Genético , Proteínas Protozoarias/análisis , Técnica del ADN Polimorfo Amplificado Aleatorio/veterinaria , Alineación de SecuenciaRESUMEN
Severe combined immunodeficient (SCID)-beige mice inoculated with the intracellular parasite Eimeria papillata produced significantly more oocysts during primary infections than inoculated immunodeficient SCID mice. Therefore, the addition of the beige mutation, which detrimentally affects neutrophil and natural killer (NK) cell functions, enhanced the parasites' ability to reproduce within the small intestine. To identify which of these two cell types is responsible for a protective immune response during primary infection, the following groups of mice were inoculated: (i) SCID mice depleted of neutrophils with antigranulocyte monoclonal antibody (RB6-8C5), (ii) C57BL/6 mice depleted of NK cells with the anti-NK-1.1 monoclonal antibody (PK136), and (iii) transgenic Tg epsilon26++ mice (T and NK cell deficient). To identify the mechanisms of immunity during primary and secondary infections, gamma interferon (IFN-gamma) knockout and perforin knockout mice were inoculated. Oocyst output was found to be significantly higher during primary infection for mice depleted of NK cells by administration of anti-NK-1.1 antibodies, for Tg epsilon26++ mice, and for IFN-gamma knockout mice. During secondary infections, only perforin knockout mice produced significantly more oocysts compared to control mice. Our observations suggest that NK cells inhibit E. papillata oocyst output during primary infection by the production of IFN-gamma and that this inhibition is independent of perforin. Immunity to reinfection does not require IFN-gamma but appears to be mediated, at least in part, by a perforin-dependent mechanism.
Asunto(s)
Coccidiosis/inmunología , Eimeria , Animales , Linfocitos T CD8-positivos/inmunología , Inmunidad Innata , Interferón gamma/fisiología , Células Asesinas Naturales/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones SCID , Neutrófilos/inmunologíaRESUMEN
Factors associated with immune-mediated protection against coccidial parasites were examined in a series of experiments utilizing immunocompromised scid/scid(SCID) and scid/scid.beige/beige(SCID/Bg) mice, as well as immunocompetent BALB/c mice. Number of oocysts produced per g feces each day and prepatent and patent periods were assessed for 4 eimerian parasites (Eimeria papillata, Eimeria vermiformis, Eimeria falciformis, and Eimeria ferrisi) using the 3 murine strains. The number of infections required to elicit a protective immune response was also determined for each coccidial species in BALB/c mice. We report the first description of patent infections in inbred immunocompetent and immunodeficient mice infected with E. papillata. Results indicate that during primary infections, parasite replication is under partial immunological control for all Eimeria species. However, the control is mechanistically different for E. papillata because the adaptive immune response does not contribute to the control of primary infections. Both coccidial species infecting intestinal villar epithelial cells (E. papillata and E. ferrisi) were affected by the beige mutation using parasite output as an indicator, whereas E. falciformis, which infects intestinal crypt cells, is not. BALB/c mice were more resistant to challenge infections with upper intestinal parasites (E. papillata and E. vermiformis) in comparison to challenge infections with lower intestinal and cecal parasites (E. falciformis and E. ferrisi).