DNA vaccine encoding peptide P10 against experimental paracoccidioidomycosis induces long-term protection in presence of regulatory T cells.

Paracoccidioidomycosis is a granulomatous systemic mycosis endemic in Brazil and other Latin America countries. A DNA vaccine encoding the immunoprotective peptide 10 (P10) significantly reduced the fungal burden in mice when given prior to or after intratracheal challenge with Paracoccidioides brasiliensis. Presently, the generation/expansion of CD4+ CD44hi memory T cells as well as Foxp3+ Treg cells in mice immunized with the DNA vaccine (pcDNA3-P10) before and after infection with P. brasiliensis was investigated. Memory CD4+ CD44hi T cells simultaneously with Foxp3+ Treg cells increased in the spleens and lungs of pcDNA3-P10 immunized mice on day 0, 30, 60 and 120 postinfection. Histopathology of the lung tissue showed minimal inflammation in immunized mice compared with the unimmunized group, suggesting a role for regulatory T cells in controlling the immunopathology. The DNA vaccine shows that the repeated immunization generates memory cells and regulatory T cells that replace the initially protective pro-inflammatory T cells conferring a long term protection while preserving the integrity of the infected tissue.

Leukotrienes are potent adjuvant during fungal infection: effects on memory T cells.

Leukotrienes (LTs) are potent lipid mediators involved in the control of host defense. LTB(4) induces leukocyte accumulation, enhances phagocytosis and bacterial clearance, and increases NO synthesis. LTB(4) is also important in early effector T cell recruitment that is mediated by LTB(4) receptor 1, the high-affinity receptor for LTB(4). The aims of this study were to evaluate whether LTs are involved in the secondary immune response to vaccination in a murine model of Histoplasma capsulatum infection. Our results demonstrate that protection of wild-type mice immunized with cell-free Ags from H. capsulatum against histoplasmosis was associated with increased LTB(4) and IFN-gamma production as well as recruitment of memory T cells into the lungs. In contrast, cell-free Ag-immunized mice lacking 5-lipoxygenase(-/-), a critical enzyme involved in LT synthesis, displayed a marked decrease on recruitment of memory T cells to the lungs associated with increased synthesis of TGF-beta as well as IL-10. Strikingly, these effects were associated with increased mortality to 5-lipoxygenase(-/-)-infected mice. These data establish an important immunomodulatory role of LTs, in both the primary and secondary immune responses to histoplasmosis.

Aseptic cure of pulmonary paracoccidioidomycosis can be achieved after a previous subcutaneous immunization of susceptible but not resistant mice.

The murine model of paracoccidioidomycosis, the most important South American endemic mycosis, mimics the human disease: resistance is associated with preserved cellular immunity while T-cell anergy is related with susceptibility. In the present study we asked whether a previous s.c. infection which induces strong cellular immunity would protect mice against a lethal pulmonary challenge. It was found that susceptible but not resistant mice developed immunoprotection and aseptic cure of infection. Immunoprotection led to reversal of DTH anergy, increased levels of antibodies and pulmonary IL-12, IL-2 and IL-4 indicating a balanced type 1/type 2 response. On the contrary, no marked differences in A/Sn infection and immunity were observed. Depletion experiments showed that immunoprotection required the cooperative action of CD4(+) and CD8(+) T cells in association with IFN-gamma and IL-12. Altogether, these observations demonstrated that susceptible hosts can develop sterilizing immunity and defined the main immunological requirements to control secondary paracoccidioidomycosis.

A propósito de las micosis pulmonares / In relation to of pulmonary mycosis

Se plantea que las micosis pulmonares son infecciones reemergentes en nuestros días, por el creciente número de individuos inmunodeprimidos (transplantados, hemopatías malignas, tratamientos oncológicos intensos, tratamientos esteroides, SIDA, etc.). Parece ser que la neutropenia severa es el factor principal para adquirir este tipo de infecciones. Cada día se encuentran nuevos microorganismos de este género implicados en una sepsis pulmonar o sistémica, de los ya conocidos patógenos oportunistas; Trichosporon, Pseudalescheria, Peniciluim, y hasta Malassezia furfur integran la larga lista de micosis profunda. Las formas de presentación clínica de las neumomicosis en estos enfermos se caraterizan por una evolución aguda o subaguda que da al traste con la vida, aun con un diganóstico precoz. Se dispone de las mismas armas diagnósticas y terapéuticas de hace 20 años, no obstante, se hacen esfuerzos en ese sentido con discretos pasos de avance, como el uso de marcadores serológicos más específicos (LPA, ácido nucleico y PCR), la TAC de alta resolución, el rescate de técnicas diagnósticas invasivas, nuevas tiazoles y fórmulas lipídicas de anfotericín B, que en combinación con la cirugía pretende disminuir la elevada mortalidad que presentan en el momento actual estas infecciones. Nos motivamos a hacer una revisión del tema con los reportes de literatura más reciente, que le ofrecemos en este artículo(AU)

A propósito de las micosis pulmonares / In relation to of pulmonary mycosis

Se plantea que las micosis pulmonares son infecciones reemergentes en nuestros días, por el creciente número de individuos inmunodeprimidos (transplantados, hemopatías malignas, tratamientos oncológicos intensos, tratamientos esteroides, SIDA, etc.). Parece ser que la neutropenia severa es el factor principal para adquirir este tipo de infecciones. Cada día se encuentran nuevos microorganismos de este género implicados en una sepsis pulmonar o sistémica, de los ya conocidos patógenos oportunistas; Trichosporon, Pseudalescheria, Peniciluim, y hasta Malassezia furfur integran la larga lista de micosis profunda. Las formas de presentación clínica de las neumomicosis en estos enfermos se caraterizan por una evolución aguda o subaguda que da al traste con la vida, aun con un diganóstico precoz. Se dispone de las mismas armas diagnósticas y terapéuticas de hace 20 años, no obstante, se hacen esfuerzos en ese sentido con discretos pasos de avance, como el uso de marcadores serológicos más específicos (LPA, ácido nucleico y PCR), la TAC de alta resolución, el rescate de técnicas diagnósticas invasivas, nuevas tiazoles y fórmulas lipídicas de anfotericín B, que en combinación con la cirugía pretende disminuir la elevada mortalidad que presentan en el momento actual estas infecciones. Nos motivamos a hacer una revisión del tema con los reportes de literatura más reciente, que le ofrecemos en este artículo

Long-term itraconazole prophylaxis against Aspergillus infections in thirty-two patients with chronic granulomatous disease.

We conducted a prospective, open study of oral itraconazole therapy (5 and then 10 mg/kg per day) to assess tolerance and potential efficacy in preventing fungal infections in patients with chronic granulomatous disease. Thirty-two patients were enrolled in one center between 1985 and 1991. Tolerance was excellent in all cases. Poor compliance was suspected in three cases. Two patients were excluded from efficacy analysis because itraconazole was used as part of therapy for pulmonary aspergillosis. Of 30 patients, 3 developed a fungal (Aspergillus) lung infection, an incidence 3.4/100 patient-years versus 11.5 in a historical control group that did not receive any prophylaxis (p = 0.13) and 9.55 in a historical group of patients who received daily ketoconazole prophylaxis (p = 0.19). The percentage of patients infected with Aspergillus was significantly different: 10% in the itraconazole group versus 34.4% in the untreated group (p = 0.013). These results require further evaluation through a comparative randomized trial to assess the possible benefit of itraconazole prophylaxis in patients with chronic granulomatous disease.

La coccidioidomicosis en el I.N.E.R / The coccidiodomycosis in the INER

Estudio retrospectivo de 12 enfermos con coccidioidomicosis pulmonar atendidos en el INER de 1987 a 1991. Como elementos claves en el diagnóstico se refieren los factores de riesgo y la identificación del hongo, lo cual es posible en el examen directo de la expectoración en el 75 por ciento de os casos, cifra que se eleva al 91.6 por ciento cuando las secreciones se obtienen mediante broncoscopia. Es útil la biopsia del órgano enfermo. Se ofrece una clasificación clínica del padecimiento y la experiencia obtenida con la anfotericina B, el ketoconazol y el itraconazol

Mucormycosis / ?

The term mucormycosis encompasses a distinctive group of infections caused by fungi belonging to genera within the taxonomic order Mucorales, usually Rhizopus, Absidia, Mortierella, and Mucor. These fungi are widespread in nature, subsisting on decaying vegetation and diverse organic materials. Although the fungi and spores of Mucorales show minimal intrinsic pathogenicity toward normal persons, they can initiate aggressive and fulminant infections under certain clinical conditions. Ketoacidotic diabetics are predisposed to rhinocerebral mucormycosis, whereas patients with leukemia or lymphoma are susceptible to pulmonary or disseminated infections. These infections, which often result in devastating long-diagnostic and therapeutic challanges