Respiratory Syncytial Virus Lung Infection in Infants: Immunoregulatory Role of Infected Alveolar Macrophages

Abstract

Thirteen previously healthy children with acute onset of severe lower respiratory tract signs and symptoms underwent bronchoscopy and bronchoalveolar lavage (BAL) for diagnostic purposes. BAL samples were assessed for viral, bacterial, mycobacterial, and fungal cultures. Cytospin preparations of BAL cells were assessed for expression of respiratory syncytial virus (RSV), HLA-DR, interleukin-1 beta, and tumor necrosis factor proteins. Purified alveolar macrophages from 2 RSV-infected children were assessed for viral replication. Three children had bacterial pneumonia and 6 were infected with RSV. BAL cells from RSV-infected children demonstrated viral protein expression. Alveolar macrophages were the predominant cell type recovered by BAL and demonstrated coexpression of RSV, HLA-DR, interleukin-1 beta, and tumor necrosis factor proteins. Purified alveolar macrophages from 2 RSV-infected children replicated RSV by infectious center assays. Thus, alveolar macrophages are infected by RSV in vivo and coexpress potent immunomodulatory molecules that potentially regulate the local immune response or lung injury due to this virus.

Proinflammatory cytokines and viral respiratory disease in pigs

“…IL-8 is generally thought to play a major role in RSV-induced neutrophil influx and bronchiolitis, because of excessive plasma IL-8 concentrations in severely affected patients [18]. All these cytokines have also been demonstrated in cultures of macrophages [83,127] and pulmonary epithelial cells [7,90]. In vitro experiments suggest that TNF-α and IL-1 are the main inducers of IL-8 during RSV infection [7,14].…”

Respiratory syncytial virus induces interleukin-10 by human alveolar macrophages. Suppression of early cytokine production and implications for incomplete immunity.

“…Alveolar macrophages are the major immune-effector cells resident in the airways, the site of RSV infection in vivo, and may serve as antigen-presenting cells for this virus. Both in vivo and in vitro studies demonstrate that alveolar macrophages serve as a target for RSV infection, coexpress viral proteins, HLA-DR molecules, and biologically active cell-associated IL-1 (6,7). Expression of these molecules by antigen-presenting cells serve as critical determinants to initiate an effective immune response (5).…”

“…Alveolar macrophages produce TNF-a, IL-6, and GM-CSF after in vitro infection with RSV (9,10). Although RSV infection in vivo induces alveolar macrophage expression of cell-associated TNF-a and IL-1/3 (6,7), in vitro studies demonstrate this virus: (a) causes only a transient increase in TNF-a mRNA, which is substantially less than that induced by LPS (9) (b), does not stimulate expression of type 1 (a, /3) IFN by differentiated macrophages, and (c) increases the expression of an IL-1 inhibitor (1 1, 12). Thus, RSV stimulates both stimulatory and inhibitory cytokines that may regulate an effective immune response.…”

Aumento de interleuquinas proinflamatorias y de cortisol plasmático en bronquiolitis por virus respiratorio sincicial: relación con la gravedad de la infección

“…La producción de IL-1β, IL-10 y de TNF-α fue encontrada en el ANF de los pacientes, presentando sólo IL-1β cantidades significativamente altas en pacientes más graves. La ausencia de IL-1β y de TNF-α en el plasma, se podría explicar porque ninguno de estos pacientes hizo una infección grave necesaria de ser tratada en unidad de cuidados intensivos, ya que ambas citoquinas se asocian a cuadros clínicos extremadamente severos en su evolución 30,31 . La cuantificación de interleuquinas es una téc-nica fácil de realizar (citometría de flujo o ELISA) sin embargo, la gran variabilidad individual en su producción y su corto tiempo de acción, dificulta su aplicabilidad clínica.…”