Lung αβ T-cells secrete IL-17A independent of ROR-γt expression and contribute to neutrophil-dependent lung damage during respiratory mycoplasma infection

Abstract

Abstract How Mycoplasma pneumoniae promotes airway inflammation is not fully understood. Experimental vaccines induce host damage [1]. Airway inflammation, caused by neutrophils and T-cells, is often seen in infants. Children represent 20% of the hospitalized M. pneumoniae cases reported annually in the United States [2]. Secreted by T-cells, IL-17A promotes neutrophil activation. In humans, IL-17A+ T-cells and IL-17A increase during infection with M. pneumoniae [3]. Lung lesions caused by Mycoplasma mycoides are linked to IL-17A in cattle [4]. No reports link IL-17A to neutrophil-mediated host damage. Understanding how IL-17A functions will aid in developing effective vaccines. We identify that CD3+ T-cells produce IL-17A during murine infection with Mycoplasma pulmonis. T-cells secreting IL-17A exist in the lungs before infection. These cells may contribute to neutrophil recruitment into the respiratory tract after infection. T-cells from the lungs and respiratory lymph nodes produced IL-17A alone, or together with IFN-γ. Expression of ROR-γt was not required for IL-17A production by respiratory αβ T-cells. Neutralizing IL-17A reduced host damage without impacting bacterial burden. Neutrophil-dependent lung lesions were lower in mice receiving αIL-17A antibodies. Depletion of neutrophils was more effective at reducing pathology when compared to IL-17A neutralization. The simultaneous neutralization and depletion of IL-17A and neutrophils failed to further reduce the disease characteristics studied. Neutrophils and IL-17A promote pathogenesis during respiratory mycoplasma disease. Neutrophil recruitment is not entirely dependent upon IL-17A. Exacerbated pathology may occur if IL-17A directly binds neutrophils.