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Multiple modes of cell death have been identified, each with a unique function and each induced in a setting-dependent manner. As billions of cells die during mammalian embryogenesis and daily in adult organisms, clearing dead cells and associated cellular debris is important in physiology. In this Review, we present an overview of the phagocytosis of dead and dying cells, a process known as efferocytosis. Efferocytosis is performed by macrophages and to a lesser extent by other ‘professional’ phagocytes (such as monocytes and dendritic cells) and ‘non-professional’ phagocytes, such as epithelial cells. Recent discoveries have shed light on this process and how it functions to maintain tissue homeostasis, tissue repair and organismal health. Here, we outline the mechanisms of efferocytosis, from the recognition of dying cells through to phagocytic engulfment and homeostatic resolution, and highlight the pathophysiological consequences that can arise when this process is abrogated.Development and homeostasis are dependent on rapid cell turnover, achieved by the programmed death and subsequent engulfment and breakdown of cells, a process known as efferocytosis. Defects in efferocytosis have been linked to a wide range of diseases; ongoing research therefore aims to better understand efferocytosis processes so as to uncover new therapeutic targets.

Compared to the tidy and immunologically silent death during apoptosis, necrosis seems like a chaotic and unorganized demise. However, we now recognize that there is a method to its madness, as many forms of necrotic cell death are indeed programmed and function beyond lytic cell death to support homeostasis and immunity. Inherently more immunogenic than their apoptotic counterpart, programmed necrosis, such as necroptosis, pyroptosis, ferroptosis, and NETosis, releases inflammatory cytokines and danger-associated molecular patterns (DAMPs), skewing the milieu to a pro-inflammatory state. Moreover, impaired clearance of dead cells often leads to inflammation. Importantly, these pathways have all been implicated in inflammatory and autoimmune diseases, therefore careful understanding of their molecular mechanisms can have long lasting effects on how we interpret their role in disease and how we translate these mechanisms into therapy.

Biofilms are aggregates of bacteria, in most cases, which are resistant usually to broad-spectrum antibiotics in their typical concentrations or even in higher doses. A trend of increasing multi-drug resistance in biofilms, which are responsible for emerging life-threatening nosocomial infections, is becoming a serious problem. Biofilms, however, are at various sensitivity levels to environmental factors and are versatile in infectivity depending on virulence factors. This review presents the fundamental information about biofilms: formation, antibiotic resistance, impacts on public health and alternatives to conventional approaches. Novel developments in micro-biosystems that help reveal the new treatment tools by sensing and characterization of biofilms will also be discussed. Understanding the formation, structure, physiology and properties of biofilms better helps eliminate them by the usage of appropriate antibiotics or their control by novel therapy approaches, such as anti-biofilm molecules, effective gene editing, drug-delivery systems and probiotics.

The recognition and clearance of dead cells is a process that must occur efficiently to prevent an autoimmune or inflammatory response. Recently, a process was identified wherein the autophagy machinery is recruited to pathogen-containing phagosomes, termed MAPLC3A (LC3)-associated phagocytosis (LAP), which results in optimal degradation of the phagocytosed cargo. Here, we describe the engagement of LAP upon uptake of apoptotic, necrotic, and RIPK3-dependent necrotic cells by macrophages. This process is dependent on some members of the classical autophagy pathway, including Beclin1, ATG5, and ATG7. In contrast, ULK1, despite being required for autophagy, is dispensable for LAP induced by uptake of microbes or dead cells. LAP is required for efficient degradation of the engulfed corpse, and in the absence of LAP, engulfment of dead cells results in increased production of proinflammatory cytokines and decreased production of anti-inflammatory cytokines. LAP is triggered by engagement of the TIM4 receptor by either phosphatidylserine (PtdSer)-displaying dead cells or PtdSer-containing liposomes. Therefore, the consequence of phagocytosis of dead cells is strongly affected by those components of the autophagy pathway involved in LAP.

Research has shown that interpersonal racial discrimination occurs frequently among racially minoritized individuals. Consequently, interracial dynamics are considered to be important considerations for effectively treating social anxiety among racially minoritized individuals. However, research to date has not directly examined the relations between racial discrimination, social anxiety, and interracial anxiety. The current study examined the association between racial discrimination, interracial anxiety and avoidance, and general symptoms of social anxiety. One hundred forty-four individuals who identified with a racially minoritized group completed an online battery of questionnaires on past year discrimination (Landrine et al., 2006), social anxiety (Liebowitz, 1987), and interracial anxiety and avoidance (Plant & Devine, 2003). Average self-reported social anxiety symptom scores for the sample were above clinical cut-off. Among Asian American, Latino/a/x participants, discrimination was associated interracial anxiety. Discrimination was not associated with social anxiety, and this finding was consistent across all racial groups. Further, interracial anxiety and social anxiety measures were only correlated within the Asian American subsample; interracial avoidance and social avoidance were correlated among non-White Latino/a/x. Our findings suggest that racial discrimination is not associated with social anxiety, and that interracial anxiety is not strongly correlated with a general measure of social anxiety symptoms. Therefore, it is important to assess interracial anxiety separately from social anxiety symptoms.

We report that extended exposure to broad-spectrum terahertz radiation results in specific changes in cellular functions that are closely related to DNA-directed gene transcription. Our gene chip survey of gene expression shows that whereas 89% of the protein coding genes in mouse stem cells do not respond to the applied terahertz radiation, certain genes are activated, while other are repressed. RT-PCR experiments with selected gene probes corresponding to transcripts in the three groups of genes detail the gene specific effect. The response was not only gene specific but also irradiation conditions dependent. Our findings suggest that the applied terahertz irradiation accelerates cell differentiation toward adipose phenotype by activating the transcription factor peroxisome proliferator-activated receptor gamma (PPARG). Finally, our molecular dynamics computer simulations indicate that the local breathing dynamics of the PPARG promoter DNA coincides with the gene specific response to the THz radiation. We propose that THz radiation is a potential tool for cellular reprogramming.

Autophagocytic disposal of mitochondria (mitophagy) is important for regulating inflammation. Kanneganti and colleagues show that RIP2 kinase–initiated mitophagy is critical for dampening virally triggered immunopathology. NOD2 receptor and the cytosolic protein kinase RIPK2 regulate NF-κB and MAP kinase signaling during bacterial infections, but the role of this immune axis during viral infections has not been addressed. We demonstrate that Nod2 −/− and Ripk2 −/− mice are hypersusceptible to infection with influenza A virus. Ripk2 −/− cells exhibited defective autophagy of mitochondria (mitophagy), leading to enhanced mitochondrial production of superoxide and accumulation of damaged mitochondria, which resulted in greater activation of the NLRP3 inflammasome and production of IL-18. RIPK2 regulated mitophagy in a kinase-dependent manner by phosphorylating the mitophagy inducer ULK1. Accordingly, Ulk1 −/− cells exhibited enhanced mitochondrial production of superoxide and activation of caspase-1. These results demonstrate a role for NOD2-RIPK2 signaling in protection against virally triggered immunopathology by negatively regulating activation of the NLRP3 inflammasome and production of IL-18 via ULK1-dependent mitophagy.

The skin is a highly organized first line of defense that stretches up to 1.8 m and is home to more than a million commensal bacteria. The microenvironment of skin is driven by factors such as pH, temperature, moisture, sebum level, oxidative stress, diet, resident immune cells, and infectious exposure. The skin has a high turnover of cells as it continually bares itself to environmental stresses. Notwithstanding these limitations, it has devised strategies to adapt as a nutrient-scarce site. To perform its protective function efficiently, it relies on mechanisms to continuously remove dead cells without alarming the immune system, actively purging the dying/senescent cells by immunotolerant efferocytosis. Both canonical (starvation-induced, reactive oxygen species, stress, and environmental insults) and non-canonical (selective) autophagy in the skin have evolved to perform astute due-diligence and housekeeping in a quiescent fashion for survival, cellular functioning, homeostasis, and immune tolerance. The autophagic \"homeostatic rheostat\" works tirelessly to uphold the delicate balance in immunoregulation and tolerance. If this equilibrium is upset, the immune system can wreak havoc and initiate pathogenesis. Out of all the organs, the skin remains under-studied in the context of autophagy. Here, we touch upon some of the salient features of autophagy active in the skin.

Objectives Racism-related stress is associated with significant mental health costs, necessitating the development of coping strategies to mitigate the negative sequelae. Mindfulness and valued living (MVL)–based strategies may be uniquely beneficial in addressing the negative effects of racism-related stress for people of color (POC) by decreasing internalized messages, while increasing self-compassion, coping flexibility, and engagement in values-based actions. It is imperative that clinicians applying or recommending MVL strategies to POC for coping with racism-related stress understand the complex nature of racism and, given that complexity, consider how MVL may need to be adapted to be effective. This paper offers guidance to clinicians seeking to use MVL strategies with clients of color to cope with racism-related stress. Methods We provide a brief contextual literature review on the nature of racism, mental health impacts of racism-related stress for POC, and selected models of coping with racism-related stress. We also review existing mindfulness literature in relation to coping with racism-related stress, while offering considerations for adapting MVL strategies specifically for coping with racism-related stress. Results Altogether, the research points to the promise of MVL strategies as beneficial interventions for coping with racism-related stress, although more research is warranted. We recommend that clinicians consider the suggestions outlined to present MVL strategies to clients in culturally responsive, validating ways. Conclusions Further research is needed to evaluate links between MVL strategies and mental health, and to evaluate whether discrimination-specific adaptations are beneficial in mitigating the mental health impacts of racism-related stress.

Natural killer (NK) cells play an essential role in innate immune control of poxviral infections in vivo. However, the mechanism(s) underlying NK cell activation and function in response to poxviruses remains poorly understood. In a mouse model of infection with vaccinia virus (VV), the most studied member of the poxvirus family, we identified that the Toll-like receptor (TLR) 2-myeloid differentiating factor 88 (MyD88) pathway was critical for the activation of NK cells and the control of VV infection in vivo. We further showed that TLR2 signaling on NK cells, but not on accessory cells such as dendritic cells (DCs), was necessary for NK cell activation and that this intrinsic TLR2-MyD88 signaling pathway was required for NK cell activation and played a critical role in the control of VV infection in vivo. In addition, we showed that the activating receptor NKG2D was also important for efficient NK activation and function, as well as recognition of VV-infected targets. We further demonstrated that VV could directly activate NK cells via TLR2 in the presence of cytokines in vitro and TLR2-MyD88-dependent activation of NK cells by VV was mediated through the phosphatidylinositol 3-kinase (PI3K)-extracellular signal-regulated kinase (ERK) pathway. Taken together, these results represent the first evidence that intrinsic TLR signaling is critical for NK cell activation and function in the control of a viral infection in vivo, indicate that multiple pathways are required for efficient NK cell activation and function in response to VV infection, and may provide important insights into the design of effective strategies to combat poxviral infections.