Effect of the novel influenza A (H1N1) virus in the human immune system

Introduction

The pandemic by the novel H1N1 virus has created the need to study any probable effects of that infection in the immune system of the host.

Methods

Blood was sampled within the first 2 days of the presentation of signs of infection from 10 healthy volunteers; from 18 patients of flu-like syndrome (FLS); and from 30 patients of infection by H1N1 confirmed by reverse RT-PCR. Absolute counts of subtypes of monocytes and of lymphocytes were determined after staining with monoclonal antibodies and analysis by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with various bacterial stimuli. Concentrations of TNFα, of IL-1β and of IFNγ were estimated in supernatants by an enzyme immunoassay.

Results

Mean absolute counts of CD14 monocytes of healthy volunteers, of FLS and of patients infected by the H1N1 virus were 271.1, 464.4 and 607.2%, respectively (P < 0.0001 compared with other groups). Respective values of CD4⁺/CD25⁺/CD127^- cells were 2.0, 4.7 and 9.0% (P < 0.0001 compared with other groups). Respective values of CD19 cells were 297.9, 151 and 137.9%. No differences between the three groups were found regarding CD3/CD4 lymphocytes, CD3/CD8 lymphocytes, natural killer (NK) cells and NKT cells. No differences were also found regarding the rate of apoptosis of the above subtypes. Six patients had H1N1-related pneumonia. Mean T-regulatory cells (Tregs) of H1N1-infected patients without pneumonia and with pneumonia were 6.7 and 17.8%, respectively (P = 0.034). Mean release of TNFα by phytohemagglutin-stimulated PBMCs of healthy volunteers, of FLS and of patients infected by H1N1 was 3,658.5, 1,877.3 and 874.4 pg/ml, respectively (P < 0.0001 compared with other groups). Respective release of TNFα by Streptococcus pneumoniae-stimulated PBMCs was 1,836.9, 949.9 and 478.0 pg/ml (P < 0.0001 compared with other groups). Mean respective release of IFNγ by PHA-stimulated PBMCs was 1,651.8, 1,235.1 and 1,114.3 pg/ml (P = 0.010 compared with FLS). Mean respective release of IFNγ by S. pneumoniae-stimulated PBMCs was 1,085.7, 748.1 and 709.7 pg/ml (P = 0.024 compared with FLS). No effect of other stimuli was shown on release of TNFα and of IFNγ. Release of IL-1β was not affected.

Conclusion

Infection by the H1N1 virus is accompanied by a characteristic impairment of the innate immune responses characterized by defective cytokine responses to S. pneumoniae. Alterations of the adaptive immune responses are predominated by an increase of Tregs. These findings signify a predisposition for pneumococcal infections after infection by H1N1 influenza.