Vaccination with Recombinant Microneme Proteins Confers Protection against Experimental Toxoplasmosis in Mice

Toxoplasmosis, a zoonotic disease caused by Toxoplasma gondii, is an important public health problem and veterinary concern. Although there is no vaccine for human toxoplasmosis, many attempts have been made to develop one. Promising vaccine candidates utilize proteins, or their genes, from microneme organelle of T. gondii that are involved in the initial stages of host cell invasion by the parasite. In the present study, we used different recombinant microneme proteins (TgMIC1, TgMIC4, or TgMIC6) or combinations of these proteins (TgMIC1-4 and TgMIC1-4-6) to evaluate the immune response and protection against experimental toxoplasmosis in C57BL/6 mice. Vaccination with recombinant TgMIC1, TgMIC4, or TgMIC6 alone conferred partial protection, as demonstrated by reduced brain cyst burden and mortality rates after challenge. Immunization with TgMIC1-4 or TgMIC1-4-6 vaccines provided the most effective protection, since 70% and 80% of mice, respectively, survived to the acute phase of infection. In addition, these vaccinated mice, in comparison to non-vaccinated ones, showed reduced parasite burden by 59% and 68%, respectively. The protective effect was related to the cellular and humoral immune responses induced by vaccination and included the release of Th1 cytokines IFN-γ and IL-12, antigen-stimulated spleen cell proliferation, and production of antigen-specific serum antibodies. Our results demonstrate that microneme proteins are potential vaccines against T. gondii, since their inoculation prevents or decreases the deleterious effects of the infection

Reversed halo sign in pulmonary paracoccidioidomycosis

OBJECTIVE. The purpose of this study was to evaluate the prevalence of the reversed halo sign in pulmonary paracoccidioidomycosis. MATERIALS AND METHODS. The high-resolution CT scans (1- or 2- mm collimation scans) of 148 consecutive patients with proven pulmonary paracoccidioidomycosis were reviewed to determine the prevalence of the reversed halo sign in these patients. The reversed halo sign was defined as central ground-glass opacity surrounded by a crescent or ring of consolidation. The images were reviewed by two radiologists who reached a decision by consensus. RESULTS. A reversed halo sign was found in 15 patients (10%), including 13 men and two women ranging in age from 20 to 58 years (mean, 48 years). Three patients had only one reversed halo sign, one had two lesions, and the remaining had multiple lesions. The size of the sign ranged from 10 to 50 mm (average, 20 mm). In two cases the reversed halo sign was the only finding on CT. The most common associated findings seen in the remaining 13 patients included bilateral patchy areas of ground-glass attenuation (n = 10), parenchymal bands (n = 8), and small centrilobular nodules (n = 8). Three patients underwent surgical lung biopsy. Histologically the central area of the lesions consisted of an inflammatory infiltrate in the alveolar septa, composed of macrophages, lymphocytes, plasma cells, and some giant cells, with relative preservation of the alveolar spaces. The periphery of the lesion consisted of dense and homogeneous intraalveolar cellular infiltrate. There was no evidence of organizing pneumonia. CONCLUSION. The reversed halo sign is seen in approximately 10% of patients with paracoccidioidomycosis. In these patients, this sign reflects the presence of a central area of predominantly interstitial inflammation surrounded by predominantly air-space infiltration.18461932193