Fig. 1

Immune response to CMV infection in spleen. A MCMV primarily enters the spleen through the marginal zone around 6 h p.i. where it infects ER-TR7+ stromal cells and activates the LTβR pathway, which depends on the interaction between LTβR-expressing stromal cells and LT-αβ+ B cells. Activation of the LTβR pathway induces NF-κB signaling in infected stromal cells, resulting in the production of type I interferons (IFNαβ). B At 36-48 h p.i. MCMV spreads into the red pulp and, in MCMV-sensitive strains, infiltrates the white pulp as well. pDCs from the red pulp start accumulating in the MZ, detecting MCMV via a TLR-dependent mechanism, leading to sustained production of IFNαβ locally and systemically. IFNαβ and IL-12, IL-15, and IL-18, also produced by pDCs and other immune cells, promote NK cell cytotoxicity. At 48 h p.i. there is a widespread infection in the spleen and changes in the spleen’s microarchitecture are starting to be evident. cDC1s form clusters with activated NK cells in an XCR1-dependent manner, delivering IL-12 and IL-15 to NK cells directly. Consequently, NK cells secrete GM-CSF, promoting the re-localization of cDC1 into the T cell zone of the white pulp, where they initiate the priming of CD8 T cells