Impaired immune response in severe human lower tract respiratory infection by respiratory syncytial virus

Carmen L Larrañaga1, Sandra L Ampuero, Vivian F Luchsinger

  • 1Programa de Virologia, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile. clarrana@med.uchile.cl

Insights

Severe respiratory syncytial virus (RSV) infection in infants is linked to a weakened immune response, including low T cell counts and altered cytokine levels. This suggests an impaired immune system contributes to disease severity.

Area of Science:

  • Immunology
  • Virology
  • Pediatrics

Background:

  • Respiratory syncytial virus (RSV) is a primary cause of severe lower respiratory infections in infants.
  • Infant immune responses significantly influence RSV disease severity.
  • Severe RSV is hypothesized to correlate with impaired immunity, marked by reduced T lymphocytes and plasma cytokines.

Purpose of the Study:

  • To investigate in vivo immune responses in infants hospitalized with their first RSV infection.
  • To compare immune responses based on clinical severity using cytokine and cellular analysis.
  • To identify immune markers associated with severe RSV disease in infants.

Main Methods:

  • Analysis of plasma cytokine concentrations in hospitalized infants with RSV.
  • Phenotyping of peripheral blood lymphocyte and natural killer (NK) cells.
  • Comparison of immune cell counts (CD4+, CD8+, CD19+, NK cells) and cytokine levels (IFN-γ, TNF-α, IL-17, IL-8) between RSV-infected and control infants.

Main Results:

  • Infants with RSV showed lower counts of CD4+, CD8+ T cells, CD19+ B cells, and NK cells compared to controls.
  • Severe RSV cases exhibited the lowest cell counts, particularly CD8+ T cells and non-active CD94+ NK cells.
  • RSV patients had reduced interferon-gamma and tumor necrosis factor-alpha, elevated interleukin-8, and varying interleukin-17 levels, with higher activity of CD94- NK cells.

Conclusions:

  • Severe RSV infection in infants is associated with diminished blood proinflammatory cytokine production.
  • Low CD8+ T cell counts are a hallmark of severe RSV disease.
  • Increased activity of specific NK cell subsets, independent of MHC class Ib, characterizes severe RSV infection.
Abstract

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