Severe and Persistent Depletion of Circulating Plasmacytoid Dendritic Cells in Patients with 2009 Pandemic H1N1 Infection

Abstract

BackgroundDysregulation of host immune responses plays a critical role in the pathogenesis of severe 2009 pandemic H1N1 infection. Whether H1N1 virus could escape innate immune defense in vivo remains to be investigated. The aim of this study was to evaluate the pattern of innate immune response during human 2009 H1N1 infection. We performed the enumeration of circulating myeloid dendritic cells (mDC) and plasmacytoid DC (pDC) in blood from patients with H1N1 pneumonia shortly after the onset of symptoms and during follow-up at different intervals of time. The analysis of CD4 and CD8 count, CD38 T-cell activation marker and serum cytokine/chemokine plasma levels was also done.Methodology/Principal FindingsBlood samples were collected from 13 hospitalized patients with confirmed H1N1-related pneumonia at time of admission and at weeks 1, 4, and 16 of follow-up. 13 healthy donors were enrolled as controls. In the acute phase of the disease, H1N1-infected patients exhibited a significant depletion in both circulating pDC and mDC in conjunction with a decrease of CD4 and CD8 T cell count. In addition, we found plasmatic hyperproduction of IP-10 and RANTES, whereas increase in T-cell immune activation was found at all time points. When we assessed the changes in DC count over time, we observed a progressive normalization of mDC number. On the contrary, H1N1-infected patients did not achieve a complete recovery of pDC count as values remained lower than healthy controls even after 16 weeks of follow-up.ConclusionsH1N1 disease is associated with a profound depletion of DC subsets. The persistence of pDC deficit for several weeks after disease recovery could be due to H1N1 virus itself or to a preexisting impairment of innate immunity.

Proinflammatory chemokines are major mediators of exuberant immune response associated with Influenza A (H1N1) pdm09 virus infection

“…CCL‐5/RANTES is a known mediator of inflammation . Contrary to our study, another study which measured plasma levels of CCL‐5/RANTES in A (H1N1) pdm09 did not show lower levels of CCL‐5/RANTES when compared to healthy controls . However, CCL‐5/RANTES levels were reported to be slightly lower in (H1N1) pdm09 and seasonal H3 infection earlier during the infection and was shown to be increased during the recovery period .…”

Transient decrease in human peripheral blood myeloid dendritic cells following influenza vaccination correlates with induction of serum antibody

“…To our knowledge, this is the first report to describe decreased blood myeloid DC subsets following vaccination in humans, however transient decreases in blood myeloid DCs have been observed in other conditions: 1) during acute myocardial infarction, where it is suggested that they are being recruited into the vessel wall and accumulating in atherosclerotic plaques (18–22), 2) in burn patients where it is associated with the incidence of sepsis (23), and 3) during acute viral infections including CMV (24) and pandemic H1N1 influenza (25). Additionally, following injection of the TLR7/8 agonist R-848 or the TLR9 agonist CpG-ODN in rhesus macaques, a decline in mDC were observed (26).…”

Circulating Myeloid Dendritic Cells is Decreased in the Acute Phase of Kawasaki Disease

“…Number of circulating DCs is reported to decrease in infection of certain viruses such as influenza H1N1 virus [17], cytomegalovirus [18], and dengue virus [19]. Because clinical picture of Kawasaki disease, including hematological and blood chemistry data, is not compatible with these known viral infections, these viruses should not take etiological role.…”

“…Immature DCs are activated after the capture of antigens in circulation or affected tissues, and then the activated DCs migrate through lymphatic vessels to lymphoid organs where they present processed antigens to naïve T cells [7][8][9][10]. Abnormalities of DC homeostasis have been involved in the pathophysiology of various human diseases, including autoimmune diseases [11][12][13][14][15], ischemic heart disease [16], and viral infection [17][18][19].…”