Innate and adaptive immune responses in patients with pandemic influenza A(H1N1)pdm09

Abstract

Innate and adaptive immune responses play critical roles in the body's defense against viruses. We investigated the host immune response against the 2009 pandemic H1N1 influenza virus [A(H1N1)pdm09] in patients before and after anti-influenza therapy and found that the numbers of dendritic cells and T cells were significantly reduced compared with those of a healthy control group. In contrast, the frequency of natural killer, cdT and T regulatory (T reg ) cells increased, and the concentrations of plasma interferon (IFN)-a/c and interleukin (IL-15) were significantly higher than those of the control. Following therapy the frequency of cdT and T reg cells returned to normal; the counts of myeloid dendritic and plasmacytoid dendritic cells were still lower than the control, while the concentrations of IFN-a/c and IL-15 remained high. We show that infection with A (H1N1)pdm09 was accompanied by changes in peripheral blood lymphocyte subgroups and cytokine profiles, leading to deleterious imbalances in innate and adaptive immunity.

Regulatory T cells and IL10 suppress pulmonary host defense during early-life exposure to radical containing combustion derived ultrafine particulate matter

“…Even though these studies looked at different compartments (i.e. peripheral blood versus pulmonary), they also observed an increase in the frequency of Tregs in infected patients that correlated with decreased frequencies of CD3 + , CD4 + and CD8 + T cells [37]. And in a separate study, elevated levels of IL10 in sera were positively correlated to severity of disease in patients infected with pH1N1 [38].…”

Innate Immune Sensing and Response to Influenza

“…Studies have observed an increased number of mDCs and pDCs in the nasal mucosa, but a decreased number in the peripheral blood of influenza virus-infected patients (Gill et al 2005 , 2008 ; Huang et al 2013 ), supporting the recruitment of circulating DCs to the site of infection. Furthermore, influenza virus infection induced activation of human DC subsets including CD1c + mDC1, pDC and moDCs characterized by upregulation of expression of HLA-DR, HLA-ABC, CD80, CD86, CD40, and CCR7 (Fonteneau et al 2003 ; Larsson et al 2000 ; le Nouen et al 2011 ; Osterlund et al 2005 ; Piqueras et al 2006 ; Smed-Sorensen et al 2012 ).…”

Approach to a highly-virulent emerging viral epidemic: A thought experiment and literature review

“…[8,[13][14][15] . [8,[18][19][20][21][22] . Virtually all arms of the immune system may be antagonized by viruses, including innate immunity and both types of adaptive immunity (humoral and cell-mediated).…”

“…Apoptosis may be triggered by a range of mechanisms. Interferon, paradoxically, is well-known for induction of immunopathology, both acutely and on chronic exposure[5,21,42] . Acute interferonopathies result from upregulation of death receptors and apoptosis-inducing ligands on monocytes, airway epithelial cells, and lymphocytes, while chronic type I interferonopathy results from induction of immunosuppressive cytokines like IL-10 and overexpression of PD-1 and PDL-1.…”

“…Acute interferonopathies result from upregulation of death receptors and apoptosis-inducing ligands on monocytes, airway epithelial cells, and lymphocytes, while chronic type I interferonopathy results from induction of immunosuppressive cytokines like IL-10 and overexpression of PD-1 and PDL-1. Generally-speaking, prolongation of infection and viral chronicity result in immune exhaustion, mediated through receptors such as PD-1 or CTLA-4[14,21,31,43,44] . One cannot exclude other plausible mechanisms of lymphopenia like glucocorticoids (as a physiological stress response or therapeutically), altered lymphocyte differentiation, or sequestration in lymphoid tissue[20,[44][45][46][47] .…”