Figure 8.

Endogenous RelA/p65 and c-Rel localization in MDDCs upon CD40L stimulation. Isolated monocytes from a healthy control (C+) and P2 were cultured for 8 d with GM-CSF and IL-4 to generate MDDCs. MDDCs were serum starved for 20 h before activation. MDDCs were incubated alone or activated with (A) LPS (1 μg/ml), TNF-α (20 ng/ml), and (B) cocultured with L-cells transfected with human CD40L (L-cell-hCD40L) or nontransfected L-cell line (L-cell) and fixed by incubation in 4% PFA. MDDCs were surface stained with mouse anti–human CD1a and Cy3-conjugated goat anti–mouse IgG (red) and endogenous RelA and c-Rel were stained with Alexa-488–conjugated goat anti–rabbit IgG against primary rabbit antibody (green). The nucleus was stained with DAPI (not depicted). (C) Schematic representation of cytokine production and cooperation between monocytes/dendritic cells and T cells. The IL-12/IFN-γ loop and the CD40L-activated CD40 pathway, mediating cooperation between T cells and monocyte/dendritic cells, are crucial for protective immunity to mycobacterial infection in humans. IL-12 production is controlled by both IFN-γ and CD40-NEMO-NF-κB signaling. Mutant molecules in patients with MSMD are indicated in gray. Allelic heterogeneity of the five autosomal disease-causing genes results in the definition of 12 genetic disorders. The NEMO mutations in the LZ domain mostly impair CD40-NEMO-dependent pathways and define the X-linked form of MSMD.