C57BL/6 and BALB/c mice are prototype hosts for the study of resistance and susceptibility to several infectious diseases. In many cases, resistance of C57BL/6 is due to the microbicidal effect of nitric oxide (NO) produced by macrophages in response to interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), mainly secreted by Th1 cells and macrophages, respectively. BALB/c, usually unable to give rise to Th1 lymphocytes, does not control certain infections. However, we and others have previously observed that regardless of the adaptive immune response, C57BL/6 (M-1) macrophages are far more sensitive to the stimulus of IFN-gamma-plus lipopolysaccharide (LPS) for the production of NO than are BALB/c (M-2) cells, a feature that might also account for resistance. Here, we report that the differential production of NO by M-1 and M-2 macrophages correlates with the accumulation of inducible nitric oxide synthase (iNOS) mRNA and protein, which shows that expression of iNOS is differentially regulated in M-1 and M-2 cells. The higher accumulation of iNOS mRNA in M-1 cells is independent of its stability, and, thus, it is possible that transcription of the iNOS gene in these cells may be more efficient than in M-2 cells. A remarkable finding is that the level of iNOS protein is much higher in M-1 macrophages than in M-2 cells, as compared with the mRNA levels, which makes us speculate that differential translational or posttranslational controls of iNOS gene are operative.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.