The importance of the phagocytes' innate response in resolution of the infection induced by a low virulent Candida albicans mutant.

We have reported that a Candida albicans mkc1Delta/mkc1Delta mutant, deleted in the Mkc1p mitogen-activated protein kinase, an essential element of the cell integrity signalling pathway, has reduced virulence in a murine model of systemic infection. We analyse here the immunological basis for this feature in view of its failure to vaccinate. Firstly, the influence of the Th response was analysed by infecting different knockout mice, revealing the importance of interferon-gamma in the resolution of mkc1 systemic infection. Secondly, the role of innate immunity was studied. The infection of neutropenic mice revealed that the candidacidal activity of neutrophils is crucial during the first 3 days of infection for the mutant strain. Macrophages played a critical role in the clearance of infection. Although a similar anti-Candida activity was found for both fungal strains with naïve macrophages, activated macrophages discriminated between both strains. In vitro experiments revealed that the mutant strain displayed a greater susceptibility to nitric oxide (NO), a reduced inhibitory effect on macrophage NO production and an increased capacity of macrophage stimulation by cell wall extracts. The importance of NO in systemic infection with the mutant strain was confirmed by the strong increase in the susceptibility of aminoguanidine (an iNOs inhibitor)-treated mice.

Human monoclonal antibodies against the rhesus D antigen from women with severe Rh immunization submitted to high-dose intravenous immunoglobulin treatment.

The pre- and postpartum maternal serum anti-D concentrations of 28 women with severe Rh(D) immunization who received high-dose intravenous immunoglobulin treatment has been determined. In all cases, including 1 in which the newborn was D negative, a sharp increment in the anti-D titer was observed after delivery. The specific immunoglobulin concentration rose to levels ranging from 4.7 to 204.0 micrograms/ml and, in 20% of the patients, increments of fifty times or greater were observed. Human monoclonal antibodies (hmAb) have been produced from Epstein-Barr virus-transformed lymphoblastoid B cell lines derived from 1 of these naturally hyperimmunized patients whose serum contained an anti-D-category DVI antibody. Four anti-D-secreting cell lines (97.E3.39.214, 44.E4.R1.257, E7.R1.126.83.115 and E11V.117.63; hereafter referred to as 214, 257, 115 and 63) have been established and maintained in continuous culture for periods ranging from several months to 3 years, without loss of antibody production capacity. Antibodies 115 and 214 recognize all Du samples tested at the same level as the polyclonal positive control. Antibodies 63 and 257 show a significantly lower reaction strength with some of the Du samples. Studies with D category cells showed that the DVI category was recognized only by hmAb 214. The reactivity pattern of this antibody is that of an anti-epD4, although the reaction strength varied greatly with different DIVa cell samples. Results obtained with hmAb 257 and 115 using papain-treated D category cells suggest that booth react as anti-epD6/7.(ABSTRACT TRUNCATED AT 250 WORDS)