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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Infection and apoptosis as a combined inflammatory trigger.
Miriam Beer Torchinsky1, Johan Garaude, J Magarian Blander
1Department of Medicine, Immunology Institute, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
Current Opinion in Immunology
|February 9, 2010
Summary
Innate immune cells encountering infected apoptotic cells initiate a unique response. This involves suppressing some inflammatory genes and promoting T helper-17 immunity for pathogen clearance and tissue repair.
Area of Science:
- Immunology
- Cellular Biology
- Infectious Disease
Background:
- Phagocytosis of pathogens and apoptotic cells are distinct immune processes.
- The innate immune response to infected apoptotic host cells remains poorly understood.
- This scenario presents conflicting signals from apoptotic cells and pathogens.
Purpose of the Study:
- To investigate the immune consequences of recognizing apoptotic host cells during infection.
- To elucidate the signaling pathways involved in this mixed-signal environment.
- To understand the resulting adaptive immune response.
Main Methods:
- The study likely involves analyzing immune cell responses to co-cultured infected apoptotic cells.
- Investigating the roles of nuclear receptors and Toll-like receptors (TLRs).
- Gene expression analysis to identify inflammatory gene transrepression and T helper-17 induction.
Main Results:
- Combined signals from infected apoptotic cells and pathogens lead to specific immune events.
- Transrepression of certain inflammatory-response genes occurs.
- Induction of a T helper-17 (Th17) adaptive immune response is observed.
Conclusions:
- The innate immune system integrates signals from infected apoptotic cells and pathogens.
- This integration results in a tailored Th17 response crucial for pathogen clearance.
- This response also facilitates host tissue repair following infection.
Related Concept Videos
01:17Phagocytosis of Apoptotic Cells
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:38Inflammation
Overview
01:12Chronic Inflammation: Introduction
Chronic inflammation is a prolonged, dysregulated immune response that persists for weeks to years when the inciting stimulus is difficult to eradicate or when self‑antigens drive ongoing reactivity. Morphologically, it is defined by mononuclear cell infiltration, progressive tissue destruction, and concurrent attempts at healing via angiogenesis and fibrosis. Compared with acute inflammation, edema is less prominent while cellular infiltration predominates; triggers include persistent...
01:30Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.