Impaired immune response in severe human lower tract respiratory infection by respiratory syncytial virus.
BACKGROUND
Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection in infants. The immune response plays a leading role in the severity of the disease. We hypothesized that severe RSV disease is associated with an impaired immune response characterized by low circulating T lymphocytes and plasma cytokine concentrations.


METHODS
We evaluate the in vivo immune responses of previously healthy infants with their first proven RSV-acute lower respiratory infection that required hospitalization. According to the clinical severity, defined by using a strict scoring system, the in vivo immune response was compared through the analysis of plasma cytokine values and the phenotyping of peripheral blood lymphocyte and natural killer (NK) cells.


RESULTS
Absolute blood cell counts of CD4+, CD8+, and CD19+ lymphocytes and NK cells were lower in subjects with RSV than in control infants. Lowest cell counts were observed in more severe RSV-infected infants. Significant low values were obtained in CD8+ lymphocytes (P = 0.03) and nonactive NK cells, that express CD94 antigen (P = 0.046). In contrast, activated NK cells that do not express CD94 molecules were significantly higher in RSV infected infants than in healthy controls (% of cells: P = 0.004). The interferon-gamma and tumor necrosis factor-alpha values in RSV infected patients were lower than in controls subjects. Interleukin-17 cytokine was not detected in healthy infants and the largest concentration was found in moderately ill patients as compared with severe cases (P = 0.033). RSV infection showed significantly higher interleukin-8 chemokine than in control infants (P = 0.024).


CONCLUSIONS
We propose that severe RSV infection in very young infants is associated with poor blood proinflammatory cytokine production, low counts of CD8+ T cells and with a greater activity of a group of NK cells, that are independent of the major histocompatibility complex class Ib recognition system.
Larrañaga
Carmen L
CL
Programa de Virologia, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile. clarrana@med.uchile.cl
Ampuero
Sandra L
SL
Luchsinger
Vivian F
VF
Carrión
Flavio A
FA
Aguilar
Nelson V
NV
Morales
Pamela R
PR
Palomino
María Angélica M
MA
Tapia
Lorena F
LF
Avendaño
Luis F
LF
D015703:Antigens, CD / Q000032:analysis; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology* / Q000302:isolation & purification; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000821:virology*; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015703:Antigens, CD; D016207:Cytokines