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

• Main Authors: Nithyananda Thorenoor, David S. Phelps, Padma Kala, Radhika Ravi, Andreas Floros Phelps, Todd M. Umstead, Xuesheng Zhang, Joanna Floros
• Format: Article
• Language: English
• Published: MDPI AG 2020-08-01
• Series: Microorganisms
• Subjects: pneumonia infection; surfactant protein A1 and A2; filtered air (FA); ozone (O₃)
• Online Access: https://www.mdpi.com/2076-2607/8/9/1276

Innate immune molecules, SP-A1 (6A², 6A⁴) and SP-A2 (1A⁰, 1A³), 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 <i>Klebsiella pneumoniae</i> or exposed to filtered air (FA) or ozone (O₃) prior to infection, and their survival monitored over 14 days. In response to infection alone, no gene- or sex-specific (except for 6A²) differences were observed; variant-specific survival was observed (1A⁰ > 6A⁴). In response to O₃, gene-, sex-, and variant-specific survival was observed with SP-A2 variants showing better survival in males than females, and 1A⁰ females > 1A³ 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. 1A⁰ 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.