Reprogrammed alveolar macrophages after pneumonia recovery

Community-acquired pneumonia is a widespread disease with significant morbidity and mortality. Alveolar macrophages are tissue-resident lung cells that play a crucial role in innate immunity against bacteria causing pneumonia. We hypothesized that alveolar macrophages display adaptive characteristics after resolution of bacterial pneumonia. We studied mice one to six months after self-limiting lung infection due to Streptococcus pneumoniae, the most common cause of bacterial pneumonia. Among the myeloid cells recovered from the lung, only alveolar macrophages showed long-term modifications of their surface marker phenotype. The remodeling of alveolar macrophages was: (i) long-lasting (still observed 6 months post infection), (ii) regionally localized (only observed in the affected lobe after lobar pneumonia), and (iii) associated with a macrophage-dependent enhanced lung protection to another pneumococcal serotype. Metabolomic and transcriptomic profiling revealed that alveolar macrophages of mice which recovered from pneumonia had new baseline activities and altered responses to infection. Thus, the enhanced lung protection after mild and self-limiting respiratory infection includes a profound remodeling of alveolar macrophages that is long-lasting, compartmentalized, and manifest across surface receptors, metabolites, and both resting and stimulated transcriptomes. We used microarrays to detail the global program of gene expression for mouse alveolar macrophages sorted from lungs that were naïve or infected more than a month previously, at rest and during an acute (4-hour) infection. Mouse lungs were selected with varying types of infectious history for alveolar macrophage sorting and RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain homogeneous populations of cells at each infection history stage in order to increase the resolution of how infection history influences expression profiles. To that end, we selected mice according to infectious criteria at four settings: not previously infected (Naive mice who receieved saline instead of SP19 a month previously) or previously infected twice with pneumococcus serotype 19F over a one-week interval more than a month previously (Experienced), either at rest (Control) or 4 hours into a current heterotypic infection with pneumococcus serotype 3 (SP3).