IL-10-Dependent Crosstalk between Murine Marginal Zone B Cells, Macrophages, and CD8α+ Dendritic Cells Promotes Listeria monocytogenes Infection

• Published in: Immunity (Cambridge, Mass.) Mass.), 2019-07, Vol.51 (1), p.64-76.e7
• Main Authors: 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, Eisenbarth, Stephanie C.
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Antigens, CD19 - metabolism; B-Lymphocytes - immunology; Bacterial infections; CD19 antigen; CD8 antigen; CD8 Antigens - metabolism; Cdc2 protein; Cell activation; Cell growth; Cell Line, Tumor; Crosstalk; Cytokines; Defects; Dendritic cells; Dendritic Cells - immunology; DOCK8; Gene expression; Gene Expression Regulation; Guanine; Guanine nucleotide exchange factor; Guanine Nucleotide Exchange Factors - genetics; IL-10; Immunization; Infections; iNOS; Interleukin 10; Interleukin-10 - genetics; Interleukin-10 - metabolism; Intracellular; Listeria; Listeria monocytogenes; Listeria monocytogenes - physiology; Listeriosis - immunology; Lymphocytes; Lymphocytes B; Lymphocytes T; macrophage; Macrophages; Macrophages - immunology; marginal zone B cells; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitric oxide; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase - metabolism; Nitric-oxide synthase; Nucleotides; Paracrine Communication; Priming; Software; Spleen; Spleen - immunology; Spleen - microbiology; T cell; White pulp
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2019.05.011

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. [Display omitted] •Loss of marginal zone (MZ) B cells reduces intracellular Listeria in CD8α+ cDC1s•Listeria stimulates MZ B cells to produce IL-10 via a MyD88-dependent pathway•IL-10 does not directly alter cDC1 handling of bacteria or antigen presentation•IL-10 inhibits iNOS and increases splenic macrophage intracellular bacterial burden Splenic dendritic cells (DCs), IL-10, and marginal zone (MZ) B cells each promote Listeria monocytogenes infection. Liu et al. show that these paradoxical responses are linked. IL-10 production from MZ B cells enhances the intracellular Listeria burden in DCs by inhibiting bacterial killing in MZ metallophilic macrophages. This crosstalk in the MZ promotes CD8+ T cell activation but also Listeria infection.