XCR1+ dendritic cells promote memory CD8+ T cell recall upon secondary infections with Listeria monocytogenes or certain viruses

Abstract

Alexandre et al. demonstrate the XCR1+ DCs are instrumental in memory CD8+ T cell responses to Listeria, VSV or vaccinia virus infection, but not CMV. Depending on the infection, robust memory CTL responses require cytokine- and chemokine-dependent cross-talk between XCR1+ DCs and NK cells or other IFN-γ–producing lymphocytes.

Memory CD8 + T Cells: Innate-Like Sensors and Orchestrators of Protection

“…For instance, CXCR3 is one of the most important memory T cell chemotactic receptors to mediates antigen-independent chemotaxis in response to IFN-induced chemokines CXCL9 and CXCL10 [32]. In the spleen of mice immunized and secondary challenged with the intracellular bacterium Lm , the memory CD8 + T cells undergo rapid recruitment and relocalization from the red and white pulp area to the marginal zones and formed “effector” clusters [22, 37, 38] exactly where blood bacteria are phagocytosed by resident macrophages (F4/80 + Moma-1 + ) [39, 40] and CD8α + cDCs [41, 42]. The local secretion of CXCL9 by cDCs, possibly the XCR1 + subset which express intracellular CXCL9 during recall infection [37], may initiate the formation of such clusters of IFNγ-secreting memory T and innate cells.…”

“…In the spleen of mice immunized and secondary challenged with the intracellular bacterium Lm , the memory CD8 + T cells undergo rapid recruitment and relocalization from the red and white pulp area to the marginal zones and formed “effector” clusters [22, 37, 38] exactly where blood bacteria are phagocytosed by resident macrophages (F4/80 + Moma-1 + ) [39, 40] and CD8α + cDCs [41, 42]. The local secretion of CXCL9 by cDCs, possibly the XCR1 + subset which express intracellular CXCL9 during recall infection [37], may initiate the formation of such clusters of IFNγ-secreting memory T and innate cells. However, sustained secretion of CXCL9 is most likely derived from the massive influx of Ly6C + monocytes that largely outnumber cDC and closely interact with IFNγ-producing memory T cells [22, 38].…”

“…Production of activating cytokines requires innate sensing intrinsic to specific subsets of myeloid cells [16, 17, 37, 43, 44]. cDCs [16] including XCR1 + DCs [37], blood-derived inflammatory Ly6C + monocytes [17], and F4/80 hi and/or CD169 + tissue-resident macrophages may all provide the reactivating signals to the memory CD8 + T cells during challenge infections in vivo .…”

“…Production of activating cytokines requires innate sensing intrinsic to specific subsets of myeloid cells [16, 17, 37, 43, 44]. cDCs [16] including XCR1 + DCs [37], blood-derived inflammatory Ly6C + monocytes [17], and F4/80 hi and/or CD169 + tissue-resident macrophages may all provide the reactivating signals to the memory CD8 + T cells during challenge infections in vivo . cDC, and notably CD8α + cDC, can act as Troyan horses carrying pathogens inside the spleen [41, 42, 50] thus may represent key initiators, while Ly6C + monocytes and tissue-macrophages can quickly amplify and sustain the signals and an effective immune response.…”

“…Mechanistically, the production of activating cytokines involves the inflammasomes [16, 17] (IL-18 production), MyD88 (IL-12) [51] and IRF3 [17] (type I IFN and subsequent IL-15) sensing pathways in these various innate cell types. The importance of cytokine-mediated-activation of memory CD8 + T cells was confirmed in multiple experimental systems including Lm , LCMV and VSV [16, 17, 43, 44], but also in the context of infections taking place in mucosal tissues (Sendai, Influenza, HSV) [20, 21, 36, 37, 52, 53]. Altogether these results support a model in which systemic circulating memory CD8 + T cells are the ones mostly responding to such cytokines.…”