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Published on: August 21, 2017
Ly6C(+) monocyte efferocytosis and cross-presentation of cell-associated antigens
S R Larson1,2, S M Atif1, S L Gibbings1
1Department of Pediatrics, National Jewish Health, Denver, CO, USA.
Insights
Ly6C(+) monocytes can engulf dying cells and present antigens to CD8(+) T cells, crucial functions in adaptive immunity. Efferocytosis is boosted by TLR4 and TLR7, while cross-presentation is enhanced only by TLR7.
Area of Science:
- Immunology
- Cell Biology
Background:
- Circulating Ly6C(+) monocytes migrate to lymph nodes with minimal phenotypic changes.
- Ly6C(+) monocytes are abundant in lymph nodes, especially during inflammation.
- The functional roles of these constitutively trafficking monocytes are largely unknown.
Purpose of the Study:
- To investigate the efferocytosis and cross-presentation capabilities of Ly6C(+) monocytes.
- To determine if these functions are comparable to those of Batf3(+) dendritic cells (DCs).
- To explore the impact of Toll-like receptor (TLR) activation on these functions.
Main Methods:
- Assessing efferocytosis and antigen cross-presentation by Ly6C(+) monocytes.
- Utilizing TLR4 and TLR7 agonists for monocyte activation.
- Analyzing T cell responses to antigen-presenting monocytes.
Main Results:
- Ly6C(+) monocytes intrinsically possess efferocytosis and cross-presentation abilities.
- Efferocytosis by Ly6C(+) monocytes is enhanced by both TLR4 and TLR7 activation.
- TLR7 activation, but not TLR4, enhances cross-presentation by Ly6C(+) monocytes.
- These monocytes present antigens to CD8(+) T cells.
Conclusions:
- Ly6C(+) monocytes exhibit significant functional roles in adaptive immune responses.
- These monocytes can effectively clear cellular debris and prime T cell immunity.
- TLR signaling differentially modulates efferocytosis and cross-presentation in Ly6C(+) monocytes.
Abstract:
Recently it was shown that circulating Ly6C(+) monocytes traffic from tissue to the draining lymph nodes (LNs) with minimal alteration in their overall phenotype. Furthermore, in the steady state, Ly6C(+) monocytes are as abundant as classical dendritic cells (DCs) within the draining LNs, and even more abundant during inflammation. However, little is known about the functional roles of constitutively trafficking Ly6C(+) monocytes. In this study we investigated whether Ly6C(+) monocytes can efferocytose (acquire dying cells) and cross-present cell-associated antigen, a functional property particularly attributed to Batf3(+) DCs. We demonstrated that Ly6C(+) monocytes intrinsically efferocytose and cross-present cell-associated antigen to CD8(+) T cells. In addition, efferocytosis was enhanced upon direct activation of the Ly6C(+) monocytes through its corresponding TLRs, TLR4 and TLR7. However, only ligation of TLR7, and not TLR4, enhanced cross-presentation by Ly6C(+) monocytes. Overall, this study outlines two functional roles, among others, that Ly6C(+) monocytes have during an adaptive immune response.
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