Absence of scavenger receptor A promotes dendritic cell‐mediated cross‐presentation of cell‐associated antigen and antitumor immune response

Target ablation [removal of the olfactory bulb (OBX)] induces apoptotic death of olfactory sensory neurons (OSNs) and an immune response in which activation and recruitment of macrophages (mφs) into the olfactory epithelium (OE) occupy a central role. Mφs phagocytose apoptotic neurons and secrete cytokines/growth factors that regulate subsequent progenitor cell proliferation and neurogenesis. Scavenger receptor A (SR-A) is a pattern recognition receptor that mediates binding of mφs to apoptotic cells and other relevant immune response functions. The aim of this study was to determine the impact of the absence of SR-A on the immune response to OBX. The immune response to OBX was evaluated in mice in which functional expression of the mφ scavenger receptor (MSR) was eliminated by gene disruption (MSR−/−) and wild-type (wt) mice of the same genetic background. OBX induced significant apoptotic death of mature OSNs in the two strains. However, subsequent mφ infiltration and activation and progenitor cell proliferation were significantly reduced in MSR−/− vs. wt mice. Gene expression profiling at short intervals after OBX demonstrated significant differences in temporal patterns of expression of several gene categories, including immune response genes. Many immune response genes that showed different temporal patterns of expression are related to mφ function, including cytokine and chemokine secretion, phagocytosis, and mφ maturation and activation. These studies suggest that impairment of the immune response to OBX in the OE of MSR−/− mice most likely resulted from decreased mφ adhesion and subsequent reduced infiltration and activation, with a resultant decrease in neurogenesis.

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Molecular and Cellular Mechanisms of Antitumor Immune Response Activation by Dendritic Cells

Acta Naturae ◽

10.32607/20758251-2016-8-3-17-30 ◽

2016 ◽

Vol 8 (3) ◽

pp. 17-30 ◽

Cited By ~ 7

Author(s):

O. V. Markov ◽

N. L. Mironova ◽

V. V. Vlasov ◽

M. A. Zenkova

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Antigen Processing ◽

Viral Vectors ◽

Molecular Mechanisms ◽

Antitumor Immune Response ◽

Tumor Escape ◽

Cellular Mechanisms ◽

Cross Presentation ◽

Cross Dressing

Dendritic cells (DCs) play a crucial role in the initiation and regulation of the antitumor immune response. Already , DC-based antitumor vaccines have been thoroughly explored both in animal tumor models and in clinical trials. DC-based vaccines are commonly produced from DC progenitors isolated from peripheral blood or bone marrow by culturing in the presence of cytokines, followed by loading the DCs with tumor-specific antigens, such as DNA, RNA, viral vectors, or a tumor cell lysate. However, the efficacy of DC-based vaccines remains low. Undoubtedly, a deeper understanding of the molecular mechanisms by which DCs function would allow us to enhance the antitumor efficacy of DC-based vaccines in clinical applications. This review describes the origin and major subsets of mouse and human DCs, as well as the differences between them. The cellular mechanisms of presentation and cross-presentation of exogenous antigens by DCs to T cells are described. We discuss intracellular antigen processing in DCs, cross-dressing, and the acquisition of the antigen cross-presentation function. A particular section in the review describes the mechanisms of tumor escape from immune surveillance through the suppression of DCs functions.

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