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

Immunity. 2019 Jul 16;51(1):64-76.e7. doi: 10.1016/j.immuni.2019.05.011. Epub 2019 Jun 20.

Abstract

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.

Keywords: DOCK8; IL-10; Listeria monocytogenes; T cell; dendritic cells; iNOS; macrophage; marginal zone B cells; spleen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD19 / metabolism
  • B-Lymphocytes / immunology*
  • CD8 Antigens / metabolism
  • Cell Line, Tumor
  • Dendritic Cells / immunology*
  • Gene Expression Regulation
  • Guanine Nucleotide Exchange Factors / genetics
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism*
  • Listeria monocytogenes / physiology*
  • Listeriosis / immunology*
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism
  • Paracrine Communication
  • Spleen / immunology*
  • Spleen / microbiology

Substances

  • Antigens, CD19
  • CD8 Antigens
  • CD8alpha antigen
  • Dock8 protein, mouse
  • Guanine Nucleotide Exchange Factors
  • Interleukin-10
  • Nitric Oxide Synthase