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, 198 (11), 1667-76

Differential Recruitment of Dendritic Cells and Monocytes to Respiratory Mucosal Sites in Children With Influenza Virus or Respiratory Syncytial Virus Infection

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Differential Recruitment of Dendritic Cells and Monocytes to Respiratory Mucosal Sites in Children With Influenza Virus or Respiratory Syncytial Virus Infection

Michelle A Gill et al. J Infect Dis.

Abstract

Background: Influenza virus and respiratory syncytial virus (RSV) are among the most common viruses causing infections of the lower respiratory tract in young children. Although there are important differences in the immunopathogenesis of these 2 viral pathogens, little is known about how they affect antigen-presenting cells in children with acute infections.

Methods: To characterize the immune cells that are mobilized to the respiratory tract by influenza virus and RSV, we analyzed nasal wash and blood samples obtained from children hospitalized with acute respiratory infections.

Results: Influenza virus and RSV mobilize immune cells, including myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs), to the nasal mucosa. Patients with influenza virus infection had greater numbers of mDCs, pDCs, and monocytes in nasal wash samples than did patients with RSV infection. The frequencies of respiratory tract and blood T cell subsets were not affected by infection with influenza virus or RSV. Monocyte chemoattractant protein-1 concentrations in nasal wash samples were significantly increased in patients with influenza virus infection but not in those with RSV infection. RANTES (regulated on activation, normally T cell expressed and secreted) concentrations were increased only in the blood of patients with influenza virus infection.

Conclusions: Infection with influenza virus or RSV mobilizes antigen-presenting cells to the respiratory tract. The differences in antigen-presenting cell numbers and cytokine concentrations suggest that there are distinctive, early immune responses to these 2 viruses.

Conflict of interest statement

Potential conflicts of interest: none reported.

Figures

Figure 1
Figure 1
Recruitment of myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) to the upper respiratory tract and the subsequent decrease in the numbers of these cells in the blood of patients with acute influenza virus or respiratory syncytial virus (RSV) infection. The absolute numbers of mDCs and pDCs, as determined by flow cytometry in patients with influenza virus infection, RSV infection, or no viral infection (control), are displayed in columns 1–3 of each graph, respectively. Controls are healthy, uninfected subjects. The line in the center of each box denotes the median value; the lower and upper edges of the box, the 25th and 75th percentiles, respectively; and the whiskers, the range of values that fall within 1.5 box lengths from the 25th and 75th percentiles. P values denote post hoc pairwise comparisons made using Mann-Whitney U tests with Bonferroni corrections for family-wise multiple comparisons. Numbers of CD11c+ mDCs in nasal wash (A) and blood (B) samples obtained from each patient group. Absolute numbers of pDCs in nasal wash (C) and blood (D) samples obtained from each patient group.
Figure 2
Figure 2
Increase in the number of monocytes in nasal wash samples obtained from patients with influenza. Absolute numbers of CD14+ cells (monocytes) identified by flow cytometry in the nasal wash (A) and blood (B) samples obtained from patients infected with influenza virus or respiratory syncytial virus or from control subjects. The line in the center of each box denotes the median value; the lower and upper edges of the box, the 25th and 75th percentiles respectively; and the whiskers, the range of values that fall within 1.5 box lengths from the 25th and 75th percentiles. P values denote post hoc pairwise comparisons made using Mann-Whitney U tests with Bonferroni corrections for family-wise multiple comparisons. C, Flow cytometry plot demonstrating how monocytes were identified in nasal wash samples by use of flow cytometry.
Figure 3
Figure 3
No significant alteration in the numbers of T lymphocytes in the nasal wash and blood samples obtained from patients infected with influenza virus or respiratory syncytial virus (RSV). Absolute numbers of CD3+CD4+ T cells identified by flow cytometry in the nasal wash (A) and blood (B) samples obtained from patients with influenza virus or RSV infection. The line in the center of each box denotes the median value; the lower and upper edges, the 25th and 75th percentiles, respectively; and the whiskers, the range of values that fall within 1.5 box lengths from the 25th and 75th percentiles. C, Flow cytometry plot demonstrating how CD3+CD4+ T cells were identified in nasal wash samples. CD3+CD8+ T cell numbers in nasal wash (D) and blood (E) samples obtained from patients with influenza virus or RSV infection. F, Flow cytometry plot demonstrating how CD3+CD8+ T cells were identified in blood samples. No significant differences were observed between the study groups.
Figure 4
Figure 4
Nasal wash concentrations of monocyte chemoattractant protein (MCP)–1 are increased in children with acute infection with influenza virus, whereas interleukin (IL)– 6, IL-8, macrophage inflammatory protein (MIP)–1α, interferon (IFN)– γ–inducible protein–10 (IP-10), and tumor necrosis factor (TNF)– α concentrations are increased in children with acute viral respiratory infection with influenza virus or respiratory syncytial virus (RSV). Cytokines/chemokines were significantly increased in nasal wash samples obtained from patients with viral infection (due to influenza virus or RSV), compared with controls. The line in the center of each box denotes the median value; the lower and upper edges of the box, the 25th and 75th percentiles, respectively; and the whiskers, the range of values that fall within 1.5 box lengths from the 25th and 75th percentiles. P values denote post hoc pairwise comparisons made using Mann-Whitney U tests with Bonferroni corrections for family-wise multiple comparisons. A, Increased nasal wash concentrations of MCP-1 in children with acute infection with influenza virus. B, Increased nasal wash concentrations of cytokines/chemokines in patients with acute viral respiratory infection. The increased concentrations were not significantly different between the groups infected with influenza virus and RSV.
Figure 5
Figure 5
Serum concentrations of RANTES (regulated on activation, normally T cell expressed) increased exclusively in the blood of children with influenza; interleukin (IL)–1α and interferon (IFN)– γ–inducible protein–10 (IP-10) increased in patients with both influenza virus and respiratory syncytial virus (RSV) infections. Serum concentrations of RANTES, IL-1α, and IP-10 in samples obtained from patients with influenza or RSV infection and from healthy controls are displayed. The line in the center of each box denotes the median value; the lower and upper edges of the box, the 25th and 75th percentiles, respectively; and the whiskers, the range of values that fall within 1.5 box lengths from the 25th and 75th percentiles. P values denote post hoc pairwise comparisons made using Mann-Whitney U tests with Bonferroni corrections for family-wise multiple comparisons. A–C, Comparison of serum concentrations of RANTES, IL-1α, and IP-10 between study groups, respectively.

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