In-silico immune cell deconvolution of the airway proteomes of infants with pneumonia reveals a link between reduced airway eosinophils and an increased risk of mortality

Charles J Sande; Jacqueline M Waeni; James M Njunge; Martin N Mutunga; Elijah Gicheru; Nelson K Kibinge; Agnes Gwela

In addition to eosinophils, previous studies have shown infections that cause severe pneumonia such as RSV, trigger a strong cellular response, characterised by the influx of innate immune cells 20, 21 . The initial response to infection is characterised by the airway recruitment of neutrophils, which express markers such as CD11b (ITGAM) and neutrophil granule proteins such as neutrophil elastase (ELANE) 22, 23 . Other innate immune cells such as NK cells which expressed granzyme B are recruited in the lower airway and can be detected in in the lungs of mechanically-ventilated children with very severe pneumonia 24, 25 . In addition to these cells, both myeloid and plasmacytoid dendritic cells are typically recruited into the airways of children with pneumonia in the early stages of infection 24, 26 and exhibit an activated proinflammatory phenotype 24 . Adaptive immune cells including CD4+ and CD8+ T cells are present in airway samples for children with viral pneumonia 20, 27 . During infection, airway frequencies of granzyme B-secreting, activated CD8 T cells is greater in the airways of children with severe viral pneumonia 25 . In the present study, we found that protein markers of different phenotypes of CD8 T cells were significantly elevated in the airways of children who survived pneumonia relative to those who died or well controls. Although data was not available for validation of these phenotypes in the retrospective cohort, the data suggests a role for these cells in pneumonia survival. Previous studies in mechanically ventilated children showed that the frequency of lung-associated T cells increased as children recovered from infection, suggesting that these cells are an important component of effective local immunity against pneumonia and that deficits in the airways of children with pneumonia is a significant risk factor for mortality. In summary, the present data identifies a new approach for characterising the cellular immune response to pneumonia in the airway and identified critical immune populations that appear to be critical for survival. Future studies should aim to replicate these findings in samples collected from the lower respiratory tract.