Classical splenic dendritic cell subsets, cDC1 and cDC2, from C57BL/6 mice are more potent in stimulating the Th1 immune response than those from BALB/c mice during mousepox

Abstract

Abstract Classical (conventional) dendritic cells (cDCs) specialize in presenting antigen to naïve T cells, and are divided into cDC1 (CD8α+) and cDC2 (CD11b+) subpopulations based on their lineage, surface phenotype and characteristics. Despite differences, both cDC subsets can stimulate CD4+ T cells and promote polarization toward a T helper 1 (Th1) phenotype. Many studies have shown that C57BL/6 (H-2b) and BALB/c (H-2d) mice readily mount vigorous Th1 or Th2 responses, respectively, upon infection with different infectious agents, including ectromelia virus (ECTV), responsible for mousepox in mice. In this work, we compared the ability of cDC subsets from mouse strains with different susceptibility to mousepox (C57BL/6 – resistant and BALB/c – susceptible) to stimulate the Th1 cytokine immune response during ECTV infection. Results showed that splenic cDC1 and cDC2 from BALB/c mice highly express MHC class II, CD83 and/or CD86 than those from C57BL/6 mice at 5 days post infection with ECTV. Despite higher activation status, both subsets of cDCs from BALB/c mice produce low amounts of Th1-polarizing cytokines, including IL-12 and IFN-γ, than those from C57BL/6 mice. Moreover, splenic cDC1 and cDC2 cells, from ECTV-infected C57BL/6 mice, stimulated higher proliferation and production of IFN-γ and IL-2 by allogeneic CD4+ T cells of C3H (H-2k) mice in a mixed leukocyte reaction than BALB/c mice. Both subsets of BALB/c cDCs up-regulated genes engaged in cell maturation and activation compared to C57BL/6 cDCs. Overall, our data indicate that both, cDC1 and cDC2 promote CD4+ T cell differentiation into IFN-γ-producing Th1 subset, and so ensure development of a strong cell-mediated immune response and recovery of C57BL/6 mice from mousepox.