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Anti-apoptotic genes in the survival of monocytic cells during infection
Aurelia Busca1, Mansi Saxena, Marko Kryworuchko
1Infectious Disease and Vaccine Research Centre, Children's Hospital of Eastern Ontario, Research Institute, Division of Virology.
Abstract:
Macrophages are cells of the immune system that protect organisms against invading pathogens by fulfilling critical roles in innate and adaptive immunity and inflammation. They originate from circulating monocytes and show a high degree of heterogeneity, which reflects the specialization of function given by different anatomical locations. Differentiation of monocytes towards a macrophage phenotype is also accompanied by an increase of resistance against various apoptotic stimuli, a required characteristic that allows macrophages to accomplish their function in a stressful environment.Apoptosis, a form of programmed cell death, is a tightly regulated process, needed to maintain homeostasis by balancing proliferation with cellular demise. Caspases, a family of cysteine proteases that are highly conserved in multicellular organisms, function as central regulators of apoptosis. FLIP (FLICE-inhibitory protein), anti-apoptotic members of the Bcl2 family and inhibitors of apoptosis (IAP) are the main three groups of anti-apoptotic genes that counteract caspase activation through both the extrinsic and intrinsic apoptotic pathways.Modulation of the apoptotic machinery during viral and bacterial infections, as well as in various malignancies, is a wellestablished mechanism that promotes the survival of affected cells. The involvement of anti-apoptotic genes in the survival of monocytes/macrophages, either physiological or pathological, will be described in this review. How viral and bacterial infections that target cells of the monocytic lineage affect the expression of anti-apoptotic genes is important in understanding the pathological mechanisms that lead to manifested disease. The latest therapeutic approaches that target anti-apoptotic genes will also be discussed.
Insights
This review explores how anti-apoptotic genes help monocytes and macrophages survive during infections and cancer. Understanding these mechanisms is key for developing new therapies targeting these survival pathways.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Macrophages are crucial immune cells originating from monocytes, exhibiting functional heterogeneity based on location.
- Macrophage differentiation enhances resistance to apoptosis, essential for function in stressful environments.
- Apoptosis, or programmed cell death, is tightly regulated by caspases and counteracted by anti-apoptotic genes like FLIP, Bcl2 family members, and IAPs.
Purpose of the Study:
- To review the role of anti-apoptotic genes in monocyte/macrophage survival.
- To examine how viral and bacterial infections modulate anti-apoptotic gene expression in monocytic cells.
- To discuss current and emerging therapeutic strategies targeting anti-apoptotic genes.
Main Methods:
- Literature review of studies on apoptosis, anti-apoptotic genes, and monocytic cells.
- Analysis of mechanisms by which infections influence anti-apoptotic gene expression.
- Synthesis of information on therapeutic interventions targeting these pathways.
Main Results:
- Anti-apoptotic genes are critical for physiological and pathological survival of monocytes/macrophages.
- Infections can manipulate apoptotic machinery, promoting cell survival.
- Dysregulation of these genes contributes to disease pathogenesis.
Conclusions:
- Modulation of anti-apoptotic genes is a key survival strategy for monocytes/macrophages.
- Understanding these pathways offers insights into infection and malignancy.
- Targeting anti-apoptotic genes presents a promising therapeutic avenue.
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