NF kappa B regulator Bcl3 controls development and function of classical dendritic cells required for resistance to <i>Toxoplasma gondii</i>

Abstract The atypical IκB family member Bcl3 associates with p50/NF-κB1 or p52/NF-κB2 homodimers in the nucleus, and positively negatively modulates transcription a context-dependent manner. Since expression dendritic cells (DC) is pivotal for antigen presentation since classical DCs (cDC) are major presenting cells, we investigated role of specifically cDCs vivo by crossing Zbtb46 cre mice Bcl3flx/flx mice. were as susceptible to lethal T. gondii infection total Bcl3−/− generated poor Th1 immune responses. Consistent this, compared wildtype controls, splenic Xcr1+ Bcl3-deficient cDC1 defective Ova OT-I both Ova257–264 peptide after Ovalbumin-expressing gondii. Moreover, CD4+ CD8+ T from infected exhibited decreased gondii-specific priming revealed reduced cytokine production tetramer staining. splenocyte single cell RNA seq (scRNAseq) Bcl3-dependent genes involved processing cDCs. We also identified scRNAseq, unique hybrid subpopulation Zbtb46+ co-expressing monocyte/macrophage factor Lysozyme M. Likewise, flow cytometry two gondii-induced subpopulations cDC2 expressing markers, designated icDC1 icDC2. Together, our results indicate that determinant protective responses survival gondii-infection.