Cellular immune activation in children with acute dengue virus infections is modulated by apoptosis

Khin S Myint1, Timothy P Endy, Duangrat Mongkolsirichaikul

  • 1Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.

Insights

Apoptosis, programmed cell death, is elevated in children with severe dengue hemorrhagic fever (DHF) compared to dengue fever (DF). This finding highlights apoptosis

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Apoptosis regulates immune responses during systemic viral infections.
  • CD95 is a key mediator of apoptosis.

Purpose of the Study:

  • To investigate peripheral-blood mononuclear cell (PBMC) apoptosis and soluble CD95 levels in children with dengue virus (DV) infections.
  • To correlate apoptosis levels with dengue disease severity.

Main Methods:

  • Prospective study of children with DV infections.
  • Sequential sampling for PBMC apoptosis and plasma soluble CD95 levels.
  • Analysis of apoptotic cell populations, including CD8(+) T lymphocytes.

Main Results:

  • Higher PBMC apoptosis levels were observed during defervescence in children with dengue hemorrhagic fever (DHF) compared to dengue fever (DF) and other febrile illnesses.
  • CD8(+) T lymphocytes constituted a significant portion of apoptotic PBMCs in DHF and DF.
  • Maximum plasma soluble CD95 levels were elevated in children with DHF compared to DF.
  • PBMC apoptosis levels correlated positively with dengue disease severity.

Conclusions:

  • Apoptosis plays a role in modulating innate and adaptive immune responses during DV infection.
  • Elevated apoptosis and soluble CD95 are associated with severe dengue illness.
  • Apoptosis may be involved in the pathogenesis of viral hemorrhagic fevers.

Related Concept Videos

The Extrinsic Apoptotic Pathway01:17

The 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...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
Apoptosis01:30

Apoptosis

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.
Cellular Injury IlI: Cellular Death01:11

Cellular Injury IlI: Cellular Death

Cell death is the irreversible loss of cellular structure and function, representing the final stage of severe injury. It plays a key role in both normal physiology and disease.Types of Cell DeathThe two main types are necrosis and apoptosis, though others like necroptosis and pyroptosis also exist.Necrosis:Necrosis is an unregulated form of cell death caused by severe injury such as trauma, toxins, or ischemia. It is characterized by cell swelling, membrane loss, rupture, and leakage of...