Impact of Surfactant Protein-A Variants on Survival in Aged Mice in Response to Klebsiella pneumoniae Infection and Ozone: Serendipity in Action

Innate immune molecules, SP-A1 (6A(2), 6A(4)) and SP-A2 (1A(0), 1A(3)), differentially affect young mouse survival after infection. Here, we investigated the impact of SP-A variants on the survival of aged mice. hTG mice carried a different SP-A1 or SP-A2 variant and SP-A-KO were either infected with Klebsiella pneumoniae or exposed to filtered air (FA) or ozone (O(3)) prior to infection, and their survival monitored over 14 days. In response to infection alone, no gene- or sex-specific (except for 6A(2)) differences were observed; variant-specific survival was observed (1A(0) > 6A(4)). In response to O(3), gene-, sex-, and variant-specific survival was observed with SP-A2 variants showing better survival in males than females, and 1A(0) females > 1A(3) females. A serendipitous, and perhaps clinically important observation was made; mice exposed to FA prior to infection exhibited significantly better survival than infected alone mice. 1A(0) provided an overall better survival in males and/or females indicating a differential role for SP-A genetics. Improved ventilation, as provided by FA, resulted in a survival of significant magnitude in aged mice and perhaps to a lesser extent in young mice. This may have clinical application especially within the context of the current pandemic.