Thus, CD40 induces the anti-T. gondii activity of mouse macrophages through TNF-α signaling.
This is supported by studies that revealed that scavengers of O2− and H2O2 do not affect the induction of anti-T. gondii activity in CD40-activated human and mouse macrophages (R. M. Andrade, M. Wessendarp, and C. S. Subauste, unpublished observations). Disrupting the costimulatory CD40-CD40L dyad reduces atherosclerosis, but can result in immune suppression. CD40 signaling induces macrophage anti-T. gondii activity independently of RNI.Antimicrobial activity mediated by NOS2 activation and production of RNI is a hallmark of IFN-γ-activated mouse macrophages. [8] Consistent with its widespread expression on normal cells, CD40 is also expressed on a wide range of tumor cells, including non-Hodgkin's and Hodgkin's lymphomas, myeloma and some carcinomas including nasopharynx, bladder, cervix, kidney and ovary. Flow cytometric analysis confirmed that only activated T cells expressed CD154 (data not shown). USA.gov. 2015 May;39(5):782-90. doi: 10.1038/ijo.2014.198. ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology. Unsorted and sorted CD40+ and CD40− bone marrow-derived macrophages were cultured with anti-CD40 or control MAbs. 3A) (P = 0.3, n = 3). HHS Monolayers were examined 18 h postinfection. Recombinant high-density lipoprotein (rHDL) nanoparticles were used to target TRAF-STOPs to macrophages. (B) RNA was obtained from bone marrow-derived macrophages after 6 h and used to generate cDNA. Bone marrow-derived macrophages were also plated on eight-well chamber culture slides.
Studies are under way to identify the effector mechanism by which CD40 signaling induces anti-T. gondii activity in macrophages. Similar results were obtained when lysates were collected 18 h postinfection with T. gondii (data not shown). | As shown in Fig. This receptor has been found to be essential in mediating a broad variety of immune and inflammatory responses including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation.
5). Figure 2B shows that a neutralizing anti-CD154 MAb significantly inhibited the effect of activated T cells on parasite load (82.4% ± 7.0% inhibition; P = 0.001, n = 3). Despite the evidence that macrophages are diverse in regards to the mechanisms that lead to their activation and effector functions (9, 19), gamma interferon (IFN-γ) is still considered central for the generation of macrophages with antimicrobial activity against intracellular pathogens (9, 19).
6C) (47.2% ± 5.0% inhibition; P < 0.00, n = 3). The decrease in the percentage of infected cells was not caused by selective cell loss in CD40-activated monolayers. Results of one representative experiment out of three are shown. Bands were developed using enhanced chemiluminescence following manufacturer's instructions (Pierce, Rockford, IL). For immunofluorescence and confocal microscopy, transgenic RH T. gondii that expresses yellow fluorescent protein (YFP; gift from David Roos) was used to infect resident peritoneal macrophages at a ratio of three parasites per macrophage. TRAF-STOPs are particularly effective in monocytes/macrophages and hamper monocyte recruitment, macrophage activation, and foam cell formation.
The number of cycles produced band densities that were directly proportional to the amount of cDNA amplified.