IL-10-Dependent Crosstalk between Murine Marginal Zone B Cells, Macrophages, and CD8α
Immunity 2019 Jul 16; 51(1):64-76.e7
Type 1 CD8α+ conventional dendritic cells (cDC1s) are required for CD8+ T cell priming but, paradoxically, promote splenic Listeria monocytogenes infection. Using mice with impaired cDC2 function, we ruled out a role for cDC2s in this process and instead discovered an interleukin-10 (IL-10)-dependent cellular crosstalk in the marginal zone (MZ) that promoted bacterial infection. Mice lacking the guanine nucleotide exchange factor DOCK8 or CD19 lost IL-10-producing MZ B cells and were resistant to Listeria. IL-10 increased intracellular Listeria in cDC1s indirectly by reducing inducible nitric oxide synthase expression early after infection and increasing intracellular Listeria in MZ metallophilic macrophages (MMMs). These MMMs trans-infected cDC1s, which, in turn, transported Listeria into the white pulp to prime CD8+ T cells. However, this also facilitated bacterial expansion. Therefore, IL-10-mediated crosstalk between B cells, macrophages, and cDC1s in the MZ promotes both Listeria infection and CD8+ T cell activation.
Liu, Dong; Yin, Xiangyun; Olyha, Sam J; Nascimento, Manuela Sales L; Chen, Pei; White, Theresa; Gowthaman, Uthaman; Zhang, Tingting; Gertie, Jake A; Zhang, Biyan; Xu, Lan; Yurieva, Marina; Devine, Lesley; Williams, Adam; and Eisenbarth, Stephanie C, "IL-10-Dependent Crosstalk between Murine Marginal Zone B Cells, Macrophages, and CD8α" (2019). Faculty Research 2019. 162.