Large scale comparison of innate responses to viral and bacterial pathogens in mouse and macaque

Area of Science:

• Immunology
• Infectious Diseases
• Comparative Genomics

Background:

• Lower respiratory tract infections pose significant global health risks, causing widespread morbidity and mortality.
• Alveolar macrophages are critical immune cells, acting as the initial responders to pathogens in the lungs.

Purpose of the Study:

• To compare and contrast the immune responses of mice and macaques to viral and bacterial lung pathogens.
• To identify conserved and divergent gene expression patterns in alveolar macrophages between species and across different infections.

Main Methods:

• Alveolar macrophages were profiled from mice and macaques at six time points post-infection.
• Infections included two viral (influenza A strains PR8 and Fuj/02) and two bacterial (Mycobacterium tuberculosis and Francisella tularensis Schu S4) pathogens.
• Gene expression profiles were analyzed comparatively across and between species.

Main Results:

• A conserved set of interferon response pathway genes was activated in both species and across all tested pathogens.
• Similarities were observed in how innate immune cells respond to lethal versus non-lethal infections in both mice and macaques.
• Distinct species-specific and pathogen-specific immune response patterns were also identified.

Conclusions:

• Innate immune responses to lower respiratory tract pathogens show both conserved and divergent mechanisms between mice and macaques.
• The interferon pathway represents a core conserved response across different pathogen types and host species.
• Understanding these comparative immune profiles offers new insights into host-pathogen interactions and innate immunity.