Results and Problems in Cell Differentiation最新文献

Pneumonia, as well as other types of acute and chronic lung injuries, remain the leading causes of death in individuals living with HIV. Individuals with HIV who are on antiretroviral therapy continue to have a greater risk for pneumonia, including bacterial and mycobacterial infections. Alveolar macrophages and lung epithelial cells constitute the first line of host defense against invading pathogens. The predisposition of individuals living with HIV to infections despite ante-retroviral therapy is mechanistically related to HIV pro-viruses integrating into host cells, including airway epithelial cells and alveolar macrophages. Alveolar macrophages harbor latent HIV even when individuals appear to have complete suppression on ART. In parallel, pneumonia can irreversibly impair lung function in HIV-infected individuals. Cells that Macrophages exposed to HIV or HIV-related proteins have been shown to secrete exosomes that contain miRNAs. These exosomes can regulate several innate and acquired immune functions by stimulating cytokine production and inflammatory responses. Furthermore, these secreted exosomal miRNAs can shuttle between cells, causing cellular dysfunction in the case of epithelial cells; they disrupt lung epithelial barrier dysfunction, which leads to a predisposition to bacterial infections. We discuss the common bacterial infections that occur in patients living with HIV and provide mechanistic insights into how the intercellular communication of miRNAs results in cellular dysfunction.

Macrophages are critical to the immune response, serving multiple essential roles in maintaining tissue homeostasis and providing immune protection. These cells also interact with and influence the extracellular matrix (ECM) by sensing and responding to its components. Such interactions between macrophages and the ECM are mediated through the secretion and uptake of various biomacromolecules, such as cytokines and the extracellular vesicles, including exosomes and microvesicles. These vesicles are pivotal in regulating cellular behaviors that affect the organism's overall function. Moreover, macrophages are integral to the repair mechanisms that alter tissue structure and functionality during tissue remodeling. This chapter will delineate how macrophages interact with the ECM and discuss potential therapeutic strategies leveraging these interactions. It will conclude with a discussion of the challenges ahead, highlighting the importance of understanding macrophage-ECM dynamics for advancing basic biology and clinical applications.

Among multiple pathways of intercellular communication operative in multicellular organisms, the trafficking of extracellular vesicles (EVs) and particles (EP) represents a unique mode of cellular information exchange with emerging roles in health and disease, including cancer. A distinctive feature of EV/EP-mediated cell-cell communication is that it involves simultaneous short- or long-range transfer of numerous molecular constituents (cargo) from donor to recipient cells. EV/EP uptake by donor cells elicits signalling or metabolic responses, or else leads to EV-re-emission or degradation. EVs are heterogeneous membranous structures released from cells via increasingly defined mechanisms involving either formation of multivesicular endosomes (exosomes) or budding from the plasma membrane (ectosomes). EPs (exomeres, supermeres) are membraneless complex particles, smaller than EVs and of less defined biogenesis and function. EVs/EPs carry complex assemblies of proteins, lipids and nucleic acids (RNA, DNA), which they shuttle into intercellular milieu, body fluids and recipient cells, via surface contact, fusion and different forms of internalization (endocytosis, micropinocytosis). While the physiological functions of EVs/EPs communication pathways continue to be investigated, their roles in cancer are increasingly well-defined. For example, EVs are involved in the transmission of cancer-specific molecular cargo, including mutant, oncogenic, transforming, or regulatory macromolecules to indolent, or normal cells, sometimes triggering their quasi-transformation-like states, or phenotypic alterations. Conversely, a reciprocal and avid uptake of stromal EVs by cancer cells may be responsible for modulating their oncogenic repertoire, as exemplified by the angiocrine effects of endothelial EVs influencing cancer cell stemness. EV exchanges during cancer progression have also been implicated in the formation of tumour stroma, angiogenesis and non-angiogenic neovascularization processes, immunosuppression, colonization of metastatic organ sites (premetastatic niche), paraneoplastic and systemic pathologies (thrombosis, diabetes, hepatotoxicity). Thus, an EV/EP-mediated horizontal transfer of cellular content emerges as a new dimension in cancer pathogenesis with functional, diagnostic, and therapeutic implications.

Trogocytosis, an active cellular process involving the transfer of plasma membrane and attached cytosol during cell-to-cell contact, has been observed prominently in CD4 T cells interacting with antigen-presenting cells carrying antigen-loaded major histocompatibility complex (MHC) class II molecules. Despite the inherent absence of MHC class II molecules in CD4 T cells, they actively acquire these molecules from encountered antigen-presenting cells, leading to the formation of antigen-loaded MHC class II molecules-dressed CD4 T cells. Subsequently, these dressed CD4 T cells engage in antigen presentation to other CD4 T cells, revealing a dynamic mechanism of immune communication. The transferred membrane proteins through trogocytosis retain their surface localization, thereby altering cellular functions. Concurrently, the donor cells experience a loss of membrane proteins, resulting in functional changes due to the altered membrane properties. This chapter provides a focused exploration into trogocytosis-mediated transfer of immune regulatory molecules and its consequential impact on diverse immune responses.

The sequestration of enzymes and associated processes into sub-cellular domains, called organelles, is considered a defining feature of eukaryotic cells. However, what leads to specific outcomes and allows a eukaryotic cell to function singularly is the interactivity and exchanges between discrete organelles. Our ability to observe and assess sub-cellular interactions in living plant cells has expanded greatly following the creation of fluorescent fusion proteins targeted to different organelles. Notably, organelle interactivity changes quickly in response to stress and reverts to a normal less interactive state as homeostasis is re-established. Using key observations of some of the organelles present in a plant cell, this chapter provides a brief overview of our present understanding of organelle interactions in plant cells.

Tunneling nanotubes (TNTs) are cellular connections, which represent a novel route for cell-to-cell communication. Strong evidence points to a role for TNTs in the intercellular transfer of signals, molecules, organelles, and pathogens, involving them in many cellular functions. In myeloid cells (e.g., monocytes/macrophages, dendritic cells, and osteoclasts), intercellular communication via TNT contributes to their differentiation and immune functions, by favoring material and pathogen transfer, as well as cell fusion. This chapter addresses the complexity of the definition and characterization of TNTs in myeloid cells, the different processes involved in their formation, their existence in vivo, and finally their function(s) in health and infectious diseases, with the example of HIV-1 infection.

Tunneling nanotubes (TNTs) are thin, membranous protrusions that connect cells and allow for the transfer of various molecules, including proteins, organelles, and genetic material. TNTs have been implicated in a wide range of biological processes, including intercellular communication, drug resistance, and viral transmission. In cancer, they have been investigated more deeply over the past decade for their potentially pivotal role in tumor progression and metastasis. TNTs, as cell contact-dependent protrusions that form at short and long distances, enable the exchange of signaling molecules and cargo between cancer cells, facilitating communication and coordination of their actions. This coordination induces a synchronization that is believed to mediate the TNT-directed evolution of drug resistance by allowing cancer cells to coordinate, including through direct expulsion of chemotherapeutic drugs to neighboring cells. Despite advances in the overall field of TNT biology since the first published report of their existence in 2004 (Rustom A, Saffrich R, Markovic I, Walther P, Gerdes HH, Science. 303:1007-10, 2004), the mechanisms of formation and components vital for the function of TNTs are complex and not yet fully understood. However, several factors have been implicated in their regulation, including actin polymerization, microtubule dynamics, and signaling pathways. The discovery of TNT-specific components that are necessary and sufficient for their formation, maintenance, and action opens a new potential avenue for drug discovery in cancer. Thus, targeting TNTs may offer a promising therapeutic strategy for cancer treatment. By disrupting TNT formation or function, it may be possible to inhibit tumor growth and metastasis and overcome drug resistance.

Encountering a developmental process confined to a limited time window or a restricted embryonic area, one may deem that the mechanism to activate the process occurs with such precision in temporal and spatial terms. However, in many instances, the activation mechanism is initiated in a broad time and space, but the mechanism is actuated only when repressive mechanisms are lifted. Thus, the operation of repressive processes is essential for precise developmental regulation. Repressive regulations occur at various levels. The following representative repressive regulations and their consequences at various levels will be discussed: intercellular signaling, epigenetic regulation, transcriptional regulation, and posttranscriptional regulation.

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB) was first identified in 1882 by Robert Koch, and it is estimated that this pathogen has been around for as long as 3 million years.The World Health Organization (WHO) reported that in 2022 alone an estimated 10.6 million people developed TB worldwide, making TB the world's second leading cause of death from a single infectious agent, just after coronavirus disease (COVID-19), despite TB being a preventable and usually curable disease.Moreover, epidemiological studies suggest that approximately a quarter of the global population has been infected with TB bacteria, of which 5-10% will eventually develop symptoms and TB disease. Poverty, obesity, diabetes, and alcohol use contribute to the burden of TB.Alveolar macrophages play a pivotal role in the clearance of airborne pathogenic microorganisms and are the primary target of M. tuberculosis.Macrophage activity depend on metabolism and circadian rhythmicity, and mitochondria are a central hub that coordinates the communication between metabolism, circadian rhythmicity, and the immune system.Recent evidence has thrown light on how M. tuberculosis metabolism may regulate macrophage activity and the overall host responses to M. tuberculosis infection.This chapter explores how all these biological domains relate to each other, highlighting the multidimensional nature of TB, and positioning macrophages at center stage.

Owing to its reduced bone density and higher risk for fractures, osteoporosis remains an international public health crisis. Research highlights the essential role played by macrophage polarization in osteoporosis and indicates that the balance between pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages influences bone metabolism. This review examines how M1 and M2 macrophages contribute to the development of osteoporosis and evaluates existing therapeutic approaches aimed at controlling macrophage polarization. It also describes future study areas that will allow improved management and treatment of osteoporosis.