Phagocytosis is an essential mechanism in innate immune defense, and in maintaining homeostasis to eliminate apoptotic cells or microbes, such as Mycobacterium tuberculosis, Salmonella enterica, Streptococcus pyogenes and Legionella pneumophila. After internalizing microbial pathogens via phagocytosis, phagosomes undergo a series of ‘maturation’ steps, to form an increasingly acidified compartment and subsequently fuse with the lysosome to develop into phagolysosomes and effectively eliminate the invading pathogens. Through this mechanism, phagocytes, including macrophages, neutrophils and dendritic cells, are involved in the processing of microbial pathogens and antigen presentation to T cells to initiate adaptive immune responses. Therefore, phagocytosis plays a role in the bridge between innate and adaptive immunity. However, intracellular bacteria have evolved diverse strategies to survive and replicate within hosts. In this review, we describe the sequential stages in the phagocytosis process. We also discuss the immune evasion strategies used by pathogens to regulate phagosome maturation during intracellular bacterial infection, and indicate that these might be used for the development of potential therapeutic strategies for infectious diseases.

The treatment of tumors requires the induction of cell death. Radiotherapy, chemotherapy, and immunotherapy are administered to kill cancer cells; however, some cancer cells are resistant to these therapies. Therefore, effective treatments require various strategies for the induction of cell death. Regulated cell death (RCD) is systematically controlled by intracellular signaling proteins. Apoptosis and autophagy are types of RCD that are morphologically different from necrosis, while necroptosis, pyroptosis, and ferroptosis are morphologically similar to necrosis. Unlike necrosis, regulated necrotic cell death (RNCD) is caused by disruption of the plasma membrane under the control of specific proteins and induces tissue inflammation. Various types of RNCD, such as necroptosis, pyroptosis, and ferroptosis, have been used as therapeutic strategies against various tumor types. In this review, the mechanisms of necroptosis, pyroptosis, and ferroptosis are described in detail, and a potential effective treatment strategy to increase the anticancer effects on apoptosis- or autophagy-resistant tumor types through the induction of RNCD is suggested.

Autophagy is a lysosomal self-digestion pathway that maintains internal homeostasis inside cells and critical process by which the innate immune system eliminates intracellular bacteria. In this study, we showed that stimulation of toll-like receptor 7 (TLR7) with imiquimod (IMQ) triggered autophagic cell death in macrophages by enhancing the generation of reactive oxygen species (ROS) via the p38-or MEK/ERK1/2-mediated signaling pathway in the early phase. IMQ significantly increased mitochondrial ROS and targeted autophagosomes to the mitochondria. Stimulation of TLR7 with IMQ enhanced the expression of BNIP3, which was localized to mitochondria and interacted with beclin-1, leading to mitophagy. In addition, IMQ substantially induced NO production through the GSK-3β-mediated signaling pathway, which led to autophagy in the late stage. We further examined whether the induction of autophagy by IMQ effectively eliminated intracellular microbes. Macrophages were infected with a virulent Mycobacterium tuberculosis (Mtb) strain, H37Rv, and then treated with IMQ. IMQ suppressed intracellular Mtb growth by inducing autophagy in a dose-dependent manner and increased NO production. Inhibition of autophagy using 3-methyladenine (3-MA) prevented autophagosome formation and control of intracellular Mtb growth in macrophages. These findings revealed a novel mechanism by which IMQ induces selective autophagy to promote intracellular killing machinery against Mtb infection in macrophages.

Angiotensin II receptor blockers (ARBs) are anti-hypertensive drugs that competitively inhibit the binding of angiotensin II to its receptor, resulting in blood vessel dilation and the reduction of blood pressure. These antagonists are also known as sartans, and are a group of pharmaceuticals that possess tetrazole or imidazole groups. In the present study, the anticancer and antimetastatic effects of the ARBs fimasartan, losartan, eprosartan and valsartan on the human prostate cancer PC-3, DU-145 and LNCap-LN3 cell lines were investigated in vitro. The proliferation of the prostate cancer cells was inhibited following treatment with 100 µM ARB. In particular, treatment with fimasartan resulted in marked anti-proliferative activity compared with the other ARBs. With respect to the molecular mechanism of the growth inhibition exhibited by the ARBs, 3-methyladenin (3-MA), an autophagy inhibitor, was revealed to increase the survival rate of PC-3 cells when cell death inhibitors were pretreated with fimasartan. In addition, the ARBs induced autophagy with increased expression levels of autophagy protein (Atg) 5–12, Atg 16-like-1, beclin-1 and microtubule-associated protein 1A/1B-light chain 3 (LC3). Notably, the enhanced expression of LC3-II (a 6.7-fold increase at 72 h) was observed in PC3 cells treated with fimasartan. This was supported by the observation of the time-dependent accumulation of LC3-positive foci in PC-3. In addition, a migration assay indicated that the ARBs induced anti-metastatic effects in PC-3 and DU-145 cells. The aforementioned results suggest that ARBs may induce autophagy-associated cell death and anti-metastatic activity in prostate cancer cells. Thus, ARBs may be a potential medication for patients with prostate cancer and hypertension.

Radiotherapy is widely used for the treatment of cancer patients, but tumor radioresistance presents serious therapy challenges. Tumor radioresistance is closely related to high levels of mTOR signaling in tumor tissues. Therefore, targeting the mTOR pathway might be a strategy to promote solid tumor sensitivity to ionizing radiation. Radioresistance is associated with enhanced antioxidant mechanisms in cancer cells. Therefore, examination of the relationship between mTOR signaling and antioxidant mechanism-linked radioresistance is required for effective radiotherapy. In particular, the effect of mTOR signaling on antioxidant glutathione induction by the Keap1-NRF2-xCT pathway is described in this review. This review is expected to assist in the identification of therapeutic adjuvants to increase the efficacy of radiotherapy.