LSC Abstract – Hookworm infection with nippostrongylus brasiliensis is a MyD88-TRIF independent mouse model of emphysema

Infections with the hookworm Nippostrongylus brasiliensis cause a rapid phase of pulmonary damage, immune activation, wound healing and then long term a progressive emphysematous pathology in mice. The emphysema is visible one month after the hookworm has left the lungs and was described but not further investigated in 2008. We characterized the immunological landscape from the infection, to investigate which cell types and activation pathways that are necessary for the emphysematous pathology by comparing BALB/c, C57BL/6 mice, IL-4Rα -/- and MyD88-TRIF -/- mice in time courses and long term. We could establish that the immunological activation published for day 42 post infection in BALB/c mice, reduce over time and is genotype specific. At two months post infection, only BALB/c mice had some immune activation in macrophage related transcripts Arg1 and IL-18 . We could detect strong differences in neutrophil recruitment and macrophage activation between the four tested genotypes during the time course. Importantly, however, all of the genotypes had comparable emphysematous bullae and increased alveolar spaces. We have described that the progressive emphysematous pathology in this rodent infection model is not related to the tested immune parameters. Neither the strong neutrophilia, macrophage activation nor normal wound healing is necessary for developing the long term pathology. Importantly, there are no other mouse models that develop emphysema independently of MyD88 or TRIF signalling after injury or infection (ex. smoking, hypoxia). By further investigations, this model may give us useful insight into unidentified emphysema-driving molecular pathways. This abstract has been presented previously at the European Respiratory Society9s Lung Science Conference in March 2016.