Abstract Prior pneumococcus exposure has been shown to remodel the lung landscape where alveolar macrophages undergo transcriptional changes, surface marker expression, and metabolomes, CD4+ resident memory T cells accelerate neutrophil recruitment and resident memory B cells produce antibodies that recognize different serotypes of pneumococcus. Excitingly, we have recently discovered that pneumococcus experience can provide heterologous protection as well, against infection with the completely unrelated bacteria E. coli. Mice were infected with left lobe intratracheal instillations of pneumococcus (“Experienced”) or saline (“Naïve”) at days 0 and 7. At day 35, pneumococcus experienced and naïve mice were challenged with E. coli. Pneumococcus experienced mice had lower bacterial burden in comparison to non-experienced mice 24h post infection with E. coli, and have better survival outcomes 7d post infection. Cytospins of bronchoalveolar lavage fluid showed experienced mice had decreased amounts of neutrophils at both early (4hpi) and later (24hpi) timepoints of infection. Therefore, we hypothesize pneumococcus experience alters immune resistance and tissue resilience pathways that confer protection and increased survival against mismatched pathogen. To determine if these changes in immune resistance and tissue resilience pathways were due to systemic immune effects or lung-localized effects, we utilized our heterotypic model to create two cohorts of pneumococcus left lobe-experienced mice and naïve mice, respectively. At d35, one cohort of pneumococcus experienced mice and naïve mice were intratracheally challenged with E. coli into their left lung while the second cohort was intratracheally challenged with E. coli into their right lung. Experienced mice had decreased bacterial burdens compared to naïve mice when the infection occurred in the previously infected left lung, but not when the E. coli infection was in the contralateral right lung. These data suggest that heterologous protection against E. coli is due to lung-localized effects that results from prior pneumococcus experience. To determine if cross-reactive antibodies in the airspaces are responsible for the decreased bacterial burden in experienced mice, BALF from pneumococcus experienced, E. coli experienced and naïve mice was utilized in an ELISA assay. There were no cross-reactive antibodies against E. coli in the pneumococcus-experienced lungs, suggesting a different immune mechanism is responsible for the reduced bacterial burden. Mechanisms by which immune resistance and tissue resilience pathways protect the lungs against heterologous infection remain to be determined. This abstract is funded by: none
Garcia et al. (Fri,) studied this question.