Abstract
Monocyte-derived dendritic cells (moDCs) have been shown to robustly expand during infection; however, their roles in anti-infectious immunity remain unclear. Here, we found that moDCs were dramatically increased in the secondary lymphoid organs during acute LCMV infection in an interferon-γ (IFN-γ)-dependent manner. We also found that priming by moDCs enhanced the differentiation of memory CD8+ T cells compared to differentiation primed by conventional dendritic cells (cDCs) through upregulation of Eomesodermin (Eomes) and T cell factor-1 (TCF-1) expression in CD8+ T cells. Consequently, impaired memory formation of CD8+ T cells in mice that had reduced numbers of moDCs led to defective clearance of pathogens upon rechallenge. Mechanistically, attenuated interleukin-2 (IL-2) signaling in CD8+ T cells primed by moDCs was responsible for the enhanced memory programming of CD8+ T cells. Therefore, our findings unveil a specialization of the antigen-presenting cell subsets in the fate determination of CD8+ T cells during infection and pave the way for the development of a novel therapeutic intervention on infection.
Highlights
CD8+ T cells play a dominant role in the elimination of infectious pathogens
We found that Monocyte-derived dendritic cells (moDCs) were expanded during lymphocytic choriomeningitis virus (LCMV) infection; in the case of bone marrow progenitor cells (BMPs), cMoPs differentiated into moDCs in an IFN-γdependent manner
The memory formation ability of CD8+ T cells activated by moDCs, equivalent numbers of the viable P14cDC or P14moDC were transferred into LCMV-infected recipient mice on day 8 p.i., and analyzed on day 28 post transfer (Figure 4D)
Summary
CD8+ T cells play a dominant role in the elimination of infectious pathogens. Following their primary activation, CD8+ T cells undergo a fate determination between short-lived effector cells (SLECs) or memory-precursor effector cells (MPECs) [1]. A strong TCR signal licenses CD8+ T cells to undergo effector-prone differentiation, whereas a weak TCR signal diverts the fate of activated CD8+ T cells to memory-like cells [2, 3]. T-bet and Blimp-1 have been shown to drive the fate of CD8+ T cells into effector cells, while Eomes and TCF1 are involved in differentiation into memory-like cells [1, 5,6,7]. The TCR signal strength is governed by TCR-MHC interaction and co-stimulation delivered by various antigen-presenting
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
