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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 &gt; 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 &gt; 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.

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