Transcriptional Features of TH1, TH2, and TH17 priming migratory dendritic cells - a common role for CXCR5 and Chi3l1

In a mouse infection model with the nematode Heligmosomoides polygurus (Hp), TH2 responses require CXCR5+ DC. The significance of CXCR5+ DCs in TH1 or TH17 infections is unknown. We probed the transcriptomes of migratory DCs in response to Hp (TH2), Citrobacter rodentii (Cr) (TH17), and Leishmania major (Lm) infection (BALB/c mice: TH2, C57BL/6 mice: TH1). We further parsed the transcriptomics of draining lymph node DCs to identify gene signatures associated with CXCR5+ DC. Wildtype mice were infected with Hp larvae or Cr by gavage. Irradiated mice reconstituted with a 1:1 ratio of wildtype (CD45.1) and CXCR5 deficient (CD45.2) bone marrow were infected with either Hp larvae or intradermal Lm. Migratory dendritic cells were sorted from mesenteric lymph nodes (msLN) of Hp or Cr infected mice and popliteal lymph nodes of Lm infected mice into CD103+ (cDC1) and CD11b+ (cDC2) subsets, then underwent RNA seq. In chimeric mice DC were also sorted by the congenic marker CD45. Thousands of differentially expressed genes (DEG) were found in cDC1 and cDC2 from Hp, Cr and Lm infected mice. Cxcr5 and Chi3l1 were expressed by cDC2 in Hp, Cr and Lm. In contrast, few DEG were identified between CXCR5+ and CXCR5- cDC2 during Hp or Lm infection. The most differentially expressed gene, Chi3l1, was restricted to CXCR5+ cDC2. cDC1 and cDC2 DEG differ in TH1 (B6 Lm), TH2 (Hp and BALB/c Lm) and TH17 (Cr) infection, but in all settings Cxcr5 and Chi3l1 were expressed by cDC2. CXCR5 deficient cDC2 fail to express Chi3l1.