Macroautophagy/autophagy has been implicated in cytoplasmic and viral antigen presentation on major histocompatibility complex (MHC) class II molecules. However, the role of autophagy in the presentation of phagocytized tumor-associated antigens in vivo remains unclear. Following the administration of apoptotic tumor cells and in vivo chemotherapy, mice with a dendritic cell-specific deletion of Atg5, a key autophagy gene, exhibit reduced CD4 + T-cell priming but not CD8 + cytotoxic T-cell priming. Interestingly, Atg5-deficient dendritic cells have an elevated expression of scavenger receptor CD36 and show excessive lipid accumulation. Atg5-deficient dendritic cells increased CD36-dependent phagocytosis of apoptotic tumor cells. CD36 blockade ameliorates elevated phagocytosis and increases CD4 + T-cell priming in dendritic cells; intratumoral CD36 blockade inhibits tumor growth. Our results demonstrate that Atg5 is required for proper antigen phagocytosis and presentation to MHC class II via modulation of CD36 in dendritic cells and may be a future therapeutic target for anti-tumor therapy.

Hematopoietic stem cells (HSCs) in bone marrow are pluripotent cells that can constitute the hematopoiesis system through self-renewal and differentiation into immune cells and red blood cells. To ensure a competent hematopoietic system for life, the maintenance of HSCs is tightly regulated. Although autophagy, a self-degradation pathway for cell homeostasis, is essential for hematopoiesis, the role of autophagy key protein Atg5 in HSCs has not been thoroughly investigated. In this study, we found that Atg5 deficiency in hematopoietic cells causes survival defects, resulting in severe lymphopenia and anemia in mice. In addition, the absolute numbers of HSCs and multiple-lineage progenitor cells were significantly decreased, and abnormal erythroid development resulted in reduced erythrocytes in blood of Vav_ Atg5 −/− mice. The proliferation of Lin − Sca-1 + c-Kit + HSCs was aberrant in bone marrow of Vav_ Atg5 −/− mice, and mature progenitors and terminally differentiated cells were also significantly altered. Furthermore, the reconstitution ability of HSCs in bone marrow chimeric mice was significantly decreased in the presence of Atg5 deficiency in HSCs. Mechanistically, impairment of autophagy-mediated clearance of damaged mitochondria was the underlying cause of the HSC functional defects. Taken together, these results define the crucial role of Atg5 in the maintenance and the reconstitution ability of HSCs.

Antiangiogenic therapy has a clinical benefit in only a subpopulation of high-grade glioma (HGG) patients. Kim et al. show that in an orthotopic HGG model, high levels of Sox7 in tumor vessels correlate with improved survival by anti-VEGFR2 antibody, suggesting a potential mechanism of heterogeneous therapeutic outcome to antiangiogenic therapy.

Respiratory syncytial virus (RSV) is a major cause of respiratory viral infections in infants and children. Alveolar macrophages (AMs) play a crucial role in combatting airborne pathogens, strongly express CD169, and are localized in the lung alveoli. Therefore, we used CD169-diphtheria toxin receptor (DTR) transgenic mice to explore the roles of CD169+ cells in immune responses to mucosal RSV infection. The administration of diphtheria toxin to CD169-DTR mice induced specific AM depletion and reduced the recruitment of Ly6Chi monocytes. Notably, CD169+ cell depletion reduced levels of innate cytokines, such as interferon-β, IL-6, and TNF-α, in bronchoalveolar lavage fluid during RSV infection without affecting the production of proinflammatory chemokines. Moreover, the depletion of CD169+ cells increased the recruitment of inflammatory cells to the lung during the early stage of RSV infection, although not during the later stages of RSV infection. Furthermore, the depletion of CD169+ cells reduced the recruitment of effector CD8+ T cells to the lungs after RSV mucosal infection. Our findings suggest that modulating the number of CD169+ cells to enhance immune responses to RSV infection may be useful as a new therapeutic strategy.

Respiratory syncytial virus (RSV) is the leading cause of respiratory viral infection in infants and children, yet little is known about the antiviral response of plasmacytoid dendritic cells (pDCs) to RSV infection. We tracked the cellular source of interferon-β using interferon-β/yellow fluorescent protein (YFP) reporter mice and identified the signaling pathway activated by RSV that induces type I interferon production in pDCs and DCs. Results from in vitro analyses of RSV-stimulated bone marrow cells revealed that RSV induces interferon-β production in both pDCs and DCs. Kinetic analyses of interferon-β-producing cells in RSV-infected lung cells in vivo indicated that pDCs are rapidly recruited to sites of inflammation during infection. These cells produced interferon-β via the TLR7-MyD88-mediated pathway and IFNα1R-mediated pathway rather than the MAVS-mediated pathway. Moreover, pDC-ablated mice exhibited decreased interferon-γ production and the antigen specificity of CD8+ T cells. Collectively, these data indicate that pDCs play pivotal roles in cytotoxic T lymphocyte (CTL) responses and are one of producers of type I interferon during RSV infection.