The biocontrol fungus Trichoderma stromaticum downregulates respiratory burst and nitric oxide in phagocytes and IFN-gamma and IL-10.

Trichoderma stromaticum, a biocontrol agent of the cacao witches' broom pathogen Moniliophthora perniciosa, has been used in Brazil as part of the integrated pest management of cacao. At the present time, little is known about the effects of T. stromaticum on the modulation of in vitro or in vivo immune responses. The present study examined the interaction of T. stromaticum spores with cellular and molecular components of the immune system following intranasal sensitization of mice. Our results showed that T. stromaticum spores prevented the expression and production of inflammatory mediators in macrophages stimulated with interferon (IFN)-γ plus lipopolysaccharide (LPS) and neutrophils stimulated with phorbol myristate 13-acetate (PMA). Quantitative polymerase chain reaction (qPCR) assays revealed that T. stromaticum spores inhibited the expression of dectin-1 and Toll-like-receptor (TLR)2/TLR4. Intranasal injection of BALB/c mice and subsequent challenge with spores of T. stromaticum induced a discrete inflammatory response in the lungs. Interestingly, the spores inhibited local and systemic production of the regulatory IL-10 and proinflammatory IFN-γ cytokines. In addition the spores presented an antiproliferative effect on spleen cells. These findings showed that the biopesticide T. stromaticum may exert immunosuppressive effects in vitro and in vivo.

Modeling Immune Response to Leishmania Species Indicates Adenosine As an Important Inhibitor of Th-Cell Activation.

Infection by Leishmania protozoan parasites can cause a variety of disease outcomes in humans and other mammals, from single self-healing cutaneous lesions to a visceral dissemination of the parasite. The correlation between chronic lesions and ecto-nucleotidase enzymes activity on the surface of the parasite is addressed here using damage caused in epithelial cells by nitric oxide. In order to explore the role of purinergic metabolism in lesion formation and the outcome of the infection, we implemented a cellular automata/lattice gas model involving major immune characters (Th1 and Th2 cells, IFN-γ, IL-4, IL-12, adenosine-Ado-, NO) and parasite players for the dynamic analysis of the disease progress. The model were analyzed using partial ranking correlation coefficient (PRCC) to indicate the components that most influence the disease progression. Results show that low Ado inhibition rate over Th-cells is shared by L. major and L. braziliensis, while in L. amazonensis infection the Ado inhibition rate over Th-cells reaches 30%. IL-4 inhibition rate over Th-cell priming to Th1 independent of IL-12 are exclusive of L. major. The lesion size and progression showed agreement with published biological data and the model was able to simulate cutaneous leishmaniasis outcomes. The sensitivity analysis suggested that Ado inhibition rate over Th-cells followed by Leishmania survival probability were the most important characteristics of the process, with PRCC of 0.89 and 0.77 respectively. The simulations also showed a non-linear relationship between Ado inhibition rate over Th-cells and lesion size measured as number of dead epithelial cells. In conclusion, this model can be a useful tool for the quantitative understanding of the immune response in leishmaniasis.

Protective antibodies against a sphingomyelinase D from Loxosceles intermedia spider venom elicited in mice with different genetic background.

In the present investigation we used a recombinant LiD1 toxin, named rLiD1his, from Loxosceles intermedia brown spider to elicit specific antibodies in mice carrying different Human Leukocyte Antigens class II (HLAII) {DRB1.0401 (DR4), DQB1.0601 (DQ6) and DQB1.0302 (DQ8)} as well as in BALB/C and C57BL/6 control mice. All mice strains produced high antibody titers against rLiD1his but DR4 mice antibodies (the lower responder mice) were not able to recognize L. intermedia crude venom. The anti-rLiD1his sera, except from DR4 mice, were able to neutralize dermonecrotic, hemorrhagic and edematogenic effects of rLiD1his in naïve rabbits. Overlapping peptides from the amino acid sequence of LiD1 toxin were prepared by SPOT method and differences in LiD1 epitope recognition were observed using different mice anti-rLiD1his sera. The region (160)DKVGHDFSGNDDISDVGK(177) was recognized by transgenic DQ8 and DQ6 mice sera. Other epitopes were recognized by at least two different animals' sera including (10)MGHMVNAIGQIDEFVNLG(27), (37)FDDNANPEYTYHGIP(51), (70)GLRSATTPGNSKYQEKLV(87) and (259)AAYKKKFRVATYDDN(273). Among these epitopes, the epitopes 37-51 and 160-177 have already been shown in previously studies as good candidates to be used alone or combined with other peptides to induce protective immune response against Loxosceles venoms. The results presented here highlight the importance of HLAII in antibody response and recognition of specific B-cell epitopes of rLiD1his spider toxin according to HLAII type and impact in the epitopic vaccine development against this spider.

Vitamin A supplementation leads to increases in regulatory CD4+Foxp3+LAP+ T cells in mice.

Dietary compounds, including micronutrients such as vitamin A and its metabolite retinoic acid, directly influence the development and function of the immune system. In this study, we show that either dietary deficiency of or supplementation with vitamin A had immunologic effects in mice that were fed these diets during their development (for 8 wk during the postweaning period). Deficient mice presented higher levels of interferon-γ, interleukin (IL)-6, transforming growth factor-ß, IL-17, and IL-10 in the gut-associated lymphoid tissues and draining lymph nodes, indicating a proinflammatory shift in the gut mucosa. Serum immunoglobulin G levels also were elevated in these mice. Conversely, supplemented mice showed higher frequencies of CD4+Foxp3+LAP+ regulatory T cells in gut lymphoid tissues and spleen, suggesting that vitamin A supplementation in the diet may be beneficial in pathologic situations such as inflammatory bowel diseases.