72. Social stress enhances immature neutrophil release from bone marrow in murine Aspergillus fumigatus-induced allergic airway inflammation

Abstract

It is well established that stress enhances inflammation and exacerbates symptoms in diseases including asthma. Nonetheless, the mechanisms by which stress influences disease progression are unknown. Clinical cases of “severe” asthma have been associated with increased neutrophil trafficking to the lung and increased insensitivity of immune cells to the anti-inflammatory and apoptotic effects of glucocorticoids. We hypothesize that these symptoms can be exacerbated by stress and are potential mechanisms by which patients can become refractory to standard treatment and present with prolonged or dysregulated inflammation. To address this issue, we used a murine repeated social defeat (RSD) paradigm that models stress-induced exacerbation of inflammation and immune cell glucocorticoid insensitivity. For instance, previous studies in an Aspergillus fumigatus (Af) allergic airway inflammation paradigm indicate that RSD increased trafficking of glucocorticoid insensitive immune cells, increased inflammation, and delayed the resolution of inflammation in the lung. Here, we show that RSD increased production of bone marrow-derived granulocytes and increased neutrophil trafficking to the lung. Several distinct populations of neutrophils were quantified including immature neutrophils (CD16int/CD49d-), which were significantly increased in the circulation and lung of RSD and Af challenged mice. Taken together, our data indicate that the stress-induced neutrophilia in the context of allergic airway inflammation may not simply be a marker of disease, but a major factor contributing to RSD exacerbation of pulmonary inflammation and disease pathogenesis.