Antigen Cross-Presentation by Macrophages

Abstract

The contribution of dendritic cell (DC) antigen cross-presentation to the activation of CD8 + T lymphocytes for immune defense against tumors, viruses, and intracellular pathogens has been recognized widely. Although originally thought to be an exclusive characteristic of DCs, recently also other immune cells, particularly macrophages, have been shown capable of cross-presentation. Here we provide an overview of in vitro and in vivo evidence on cross-presentation by macrophages. As we discuss, it is now firmly established that various types of tissue-resident macrophages are able to cross-present via similar cellular pathways as DCs. This is based on a wide range of antigens in macrophages from many different tissue origins such as blood, tumors, and lymphoid tissue. However, the physiological relevance of macrophage cross-presentation with potential contributions to activation of CD8 + T lymphocytes is still mostly unknown. While cross-presentation by various types of proinflammatory macrophages might be involved in cross-priming of naive CD8 + T lymphocytes, it might also be involved in local reactivation of memory and/or effector CD8 + T lymphocytes. Moreover, cross-presentation by anti-inflammatory macrophages could be related to immune tolerance. Because cross-presentation promotes the initiation and potentiation of antigen-specific CD8 + T lymphocyte responses, stimulating macrophages to crosspresent antigen might be a promising strategy for antitumor or antiviral therapies.

Role of Human Leukocyte Antigen System as A Predictive Biomarker for Checkpoint-Based Immunotherapy in Cancer Patients

“…This process is necessary to recognize and destroy tumor cells as well as viruses that do not readily infect antigen-presenting cells, stimulating naïve T cells into activated CTLs [ 14 , 20 , 21 ]. Specifically, cross-presentation involves dendritic cells (DCs) which present TAAs/TSAs or pathogen-derived peptides in their HLA class I complex to naïve T cells [ 22 , 23 , 24 ]. Extracellular peptide loading on HLA class I complex differs from the canonical way followed by intracellular peptides and it will be discussed below in this review.…”

“…Extracellular peptide loading on HLA class I complex differs from the canonical way followed by intracellular peptides and it will be discussed below in this review. However, recently, several lines of evidence demonstrated that macrophages are also able to implement a cross-presentation process, subverting the original belief that it is an exclusive characteristic of DCs [ 22 ].…”

Broadly Antiviral Activities of TAP1 through Activating the TBK1-IRF3-Mediated Type I Interferon Production

“…The underlying mechanism for this phenomenon is unknown, but it is consistent with the cell biology of antigen presentation in response to TLR stimulation. TLR signaling can induce phagosomal MHC-I delivery to enhance TAP recruitment to endosomes [ 26 , 27 ], which is beneficial for antigen cross-presentation [ 28 ]. The peptide-mediated undocking of MHC class I is linked to the transport cycle of TAP1 [ 29 ].…”

Innate Immune Sensing of Viruses and Its Consequences for the Central Nervous System

“…The host’s DNA sensing of VV is complex and hence an attenuated VV strain, such as MVA or genetically engineered mice is widely used to gain insights into VV immunity. However, a limitation is that DNA sensing in mice differs from humans [ 230 , 231 ]. Several studies indicated that type I IFN production by MVA is dependent of cGAS and its downstream adaptor STING [ 227 , 232 ].…”

“…NK cells are also involved in adaptive immune response, since they cross talk with DC in several ways, including killing of immature DCs and promoting DC maturation, which leads to overall enhanced antigen presentation to T cell [ 246 ]. Similarly, macrophages also function as antigen presenting cells, thus contributing to the activation of T helper cell [ 230 ].…”