Fatal outcome of pandemic H1N1 2009 influenza infection is associated with neutrophil and macrophage lung infiltration but not enhanced viral burden in pregnant mice. (111.3)

Abstract

Abstract Pandemic H1N1 2009 Influenza A virus (pH1N1) infection in pregnant or postpartum women is quite severe. The immunological mechanisms that affect infection outcome in these populations are not well understood. To address this, pregnant Balb/c and non-pregnant mice were inoculated with a wild-type pH1N1 virus. We determined that early cytokine responses were impaired in pregnant mouse lungs. Moreover, pulmonary infiltration of neutrophils and macrophages strongly correlated with an increase in mortality in pregnant mice. Increased mortality in pregnant animals was not associated with higher virus load because equivalent viral burden (virus titers and immunohistochemical staining) was observed in the nasal cavities and lower respiratory tracts of all mice. Pregnancy altered innate responses despite the presence of similar viral burden. Also, pregnant mice demonstrated equivalent influenza-specific activation of pulmonary CD8+ T lymphocytes however; they displayed elevated T-regulator lymphocyte (Tregs) responses in the lung and mediastinal lymph nodes. Despite these immunologic alterations, pregnant animals mounted equivalent hemagglutinin inhibition and IgG subclass titers in response to virus or immunization with monovalent inactivated pH1N1 vaccine. Therefore, the severity of pH1N1 in pregnant mice is associated with pulmonary neutrophil and macrophage invasion, dysregulated cytokine responses but not increased viral load.