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The lack of antifungals with low toxicity and short-term therapy for patients with paracoccidioidomycosis (PCM) led us to evaluate adjuvants in immunotherapeutic intervention. We have previously shown complete Freund's adjuvant (CFA) to be therapeutic on experimental PCM. Owing to CFA toxicity, here we tested adjuvants approved for clinical use or in preclinical phase in experimental mouse PCM. Of all, only monophosporyl lipid A (MPLA) demonstrates a beneficial effect, by reducing the fungal burden and increasing the concentrations of IFN-γ and TNF-α, which are immunoprotective in PCM. These results suggest that MPLA might improve intervention in PCM. [ABSTRACT FROM AUTHOR]

We determined the prophylactic effect of both the d-mannose-binding lectin ArtinM extracted from the seeds of Artocarpus integrifolia (jackfruit) and its recombinant counterpart during the course of experimental paracoccidioidomycosis induced in BALB/c mice. Four experimental protocols of prophylaxis were employed to evaluate the most protective regimen of ArtinM administration. It was demonstrated that the best effect was obtained by administration of two ArtinM doses on days 10 and 3 before the challenge with Paracoccidioides brasiliensis. By following this protocol, the lungs of mice that received native or recombinant ArtinM exhibited reduced fungal burden and granuloma incidence. In addition, the protocol augmented contents of IL-12, IFN-γ, TNF-α and NO. On the other hand, the control group consisting of untreated infected mice had higher pulmonary levels of IL-4 and IL-10. In conclusion, prophylaxis with ArtinM significantly reproduces the effect of its therapeutic administration, i.e, it confers resistance to P. brasiliensis infection in mouse models by promoting IL-12 production and favours Th1-immunity. [ABSTRACT FROM AUTHOR]

The outcome and severity of some diseases correlatewith the dominance of either the T helper 1 (Th1) or Th2 immuneresponse, which is stimulated by IL-12 or IL-4, respectively. Inthe present study we demonstrate that gamma interferon (IFN-γ) secretion by murine spleen cells stimulatedwith KM+, a mannose-binding lectin from Artocarpusintegrifolia, is due to IL-12 induction, because (1) macrophagesfrom several sources (including cell lines) produced IL-12 p40 inresponse to KM+, and (2) lectin-free supernatantsfrom J774 cell line cultures stimulated with KM+ inducedthe secretion of IFN-γ by spleen cellcultures, an effect blocked by the supernatant pretreatment with anti-IL-12antibody. The known pattern of susceptibility of BALB/cmice to infection with Leishmania major, attributed to highlevels of IL-4 production leading to a Th2 nonprotective immuneresponse, was modified by administration of KM+. Draininglymph node cells from these immunized BALB/c mice (in contrastto cells from animals immunized only with soluble leishmanial antigen [SLA])secreted high levels of IFN-γ and lowlevels of IL-4, which characterized a Th1 rather than a Th2 responsepattern. The footpad thickness of BALB/c mice immunizedwith SLA plus KM+ and challenged with L.major was similar to that of uninfected mice. This beneficialeffect against leishmanial infection was blocked by pretreatmentof these mice with anti-IL-12 antibody. These observations indicatethat KM+ induces IL-12 p40 in vivo andhas a protective effect against L. major infection. [ABSTRACT FROM PUBLISHER]

Host cell invasion by Toxoplasma gondii isa multistep process with one of the first steps being the apicalrelease of micronemal proteins that interact with host receptors.We demonstrate here that micronemal protein 1 (MIC1) is a lactose-bindinglectin. MIC1 and MIC4 were recovered in the lactose-eluted (Lac+)fraction on affinity chromatography on immobilized lactose of thesoluble antigen fraction from tachyzoites of the virulent RH strain.MIC1 and MIC4 were both identified by N-terminal microsequencing. MIC4was also identified by sequencing cDNA clones isolated from an expressionlibrary following screening with mouse polyclonal anti-60/70kDa (Lac+ proteins) serum. This antiserum localizedthe Lac+ proteins on the apical region of T. gondii tachyzoites by confocal microscopy. The Lac+ fractioninduced hemagglutination (mainly type A human erythrocytes), whichwas inhibited by β-galactosides (3 mMlactose and 12 mM galactose) but not by up to 100 mM melibiose (α-galactoside), fucose, mannose, orglucose or 0.2 mg/ml heparin. The lectin activity of theLac+ preparation was attributed to MIC1, becauseblotted MIC1, but not native MIC4, bound human erythrocyte typeA and fetuin. The copurification of MIC1 and MIC4 may have beendue to their association, as reported by others. These data suggestthat MIC1 may act through its lectin activity during T.gondii infection. [ABSTRACT FROM PUBLISHER]