Role of disease-associated tolerance in infectious superspreaders

Area of Science:

• Microbiology
• Immunology
• Disease Transmission

Background:

• Disease transmission is heterogeneous, with superspreaders responsible for most infections.
• Salmonella-infected mice exhibit superspreader phenotypes, shedding high bacterial loads asymptomatically.
• Superspreader hosts display a dampened systemic immune response.

Purpose of the Study:

• To investigate the role of oral antibiotics in Salmonella-infected superspreader and non-superspreader mice.
• To elucidate the mechanisms underlying disease tolerance in superspreaders.
• To identify potential therapeutic targets for reducing morbidity associated with pathogen transmission.

Main Methods:

• Administering oral antibiotics to Salmonella-infected mice representing superspreader and non-superspreader phenotypes.
• Quantifying bacterial shedding, immune cell populations (spleen), and inflammatory markers (acute-phase proteins, cytokines).
• Neutralizing acute-phase proinflammatory cytokines to assess their impact on morbidity.

Main Results:

• Superspreader mice remained asymptomatic upon antibiotic treatment, unlike non-superspreaders who exhibited morbidity.
• Non-superspreaders showed increased splenic inflammatory myeloid cells, acute-phase proteins, and cytokines after antibiotic treatment.
• Colonic inflammation was comparable between groups, suggesting superspreader tolerance to intestinal perturbations.
• Cytokine neutralization in antibiotic-treated superspreaders reduced myeloid cell expansion and morbidity.

Conclusions:

• Superspreaders exhibit unique disease tolerance to oral antibiotics, facilitating pathogen transmission.
• Antibiotic-induced morbidity in non-superspreaders is mediated by inflammatory responses.
• Targeting acute-phase cytokines may mitigate disease severity in susceptible hosts.