Epidemiological studies have shown a correlation between chronic biomass smoke exposure and increased respiratory infection. Pulmonary macrophages are instrumental in both the innate and the adaptive immune responses to respiratory infection. In the present study, in vitro systems were utilized where alveolar macrophages (AM) and bone marrow-derived macrophages (BMdM) were exposed to concentrated wood smoke-derived particulate matter (WS-PM) and mice were exposed in vivo to either concentrated WS-PM or inhaled WS. In vivo studies demonstrated that WS-exposed mice inoculated with Streptococcus pneumoniae had a higher bacterial load 24 h post-exposure, and corresponding AM were found to have decreased lymphocyte activation activity. Additionally, while classic markers of inflammation (cellular infiltration, total protein, neutrophils) were not affected, there were changes in pulmonary macrophages populations, including significant decreases in macrophages expressing markers of activation in WS-exposed mice. The lymphocyte activation activity of WS-PM-exposed AM was significantly suppressed, but the phagocytic activity appeared unchanged. In an effort to determine a pathway for WS-induced suppression, RelB activation, assessed by nuclear translocation, was observed in AM exposed to either inhaled WS or instilled WS-PM. Finally, an analysis of WS-PM fractions determined the presence of 4–5 polycyclic aromatic hydrocarbons (PAHs), and preliminary work suggests a potential role for these PAHs to alter macrophage functions. These studies show a decreased ability of WS-exposed pulmonary macrophages to effectively mount a defense against infection, the effect lasts at least a week post-exposure, and appears to be mediated via RelB activation.

We compared growth of Streptococcus pneumoniae mutants with disruption in the pspA (PspA-), nanA (NanA-) or hyl (Hyl-) gene to the parental D39 strain using a competitive growth model in mice with and without prior influenza infection. Total bacteria numbers recovered from influenza-infected mice were significantly greater compared to mice without influenza infection. Whereas Hyl- and NanA- mutants did not display attenuation in mice with or without prior influenza infection, the PspA- mutant exhibited attenuation in mice both with and without influenza infection. This defect was severe influenza-infected mice where PspA- growth was 1800-fold less than D39. Furthermore, PspA immunization significantly reduced secondary bacterial lung burdens and specific markers of lung damage in mice receiving serotypes 2, 3 and 4 pneumococci. Our findings indicate that PspA contributes to secondary S. pneumoniae infection following influenza and that PspA immunization mitigates early secondary pneumococcal lung infections.

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