Innate immune responses yield tissue-specific bottlenecks that scale with pathogen dose.

ABSTRACT: To cause infection, pathogens must overcome bottlenecks imposed by the host immune system. These bottlenecks restrict the inoculum and largely determine whether pathogen exposure results in disease. Infection bottlenecks therefore quantify the effectiveness of immune barriers. Here, using a model of Escherichia coli systemic infection, we identify bottlenecks that tighten or widen with higher inoculum sizes, revealing that the efficacy of innate immune responses can increase or decrease with pathogen dose. We term this concept "dose scaling". During E. coli systemic infection, dose scaling is tissue specific, dependent on the lipopolysaccharide (LPS) receptor TLR4, and can be recapitulated by mimicking high doses with killed bacteria. Scaling therefore depends on sensing of p

SUBMITTER: Hullahalli K 

PROVIDER: S-EPMC10500177 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature