Untangling Cellular Host-Pathogen Encounters at Infection Bottlenecks

Bacterial pathogens can invade the tissue and establish a protected intracellular niche at the site of invasion that can spread locally (e.g., microcolonies) or to systemic sites (e.g., granulomas). Invasion of the tissue and establishment of intracellular infection are rare events that are difficult to study in the in vivo setting but have critical clinical consequences, such as long-term carriage, reinfections, and emergence of antibiotic resistance. Here, I discuss Salmonella interactions with its host macrophage during early stages of infection and their critical role in determining infection outcome. The dynamics of host-pathogen interactions entail highly heterogenous host immunity, bacterial virulence, and metabolic cross talk, requiring in vivo analysis at single-cell resolution. I discuss models and single-cell approaches that provide a global understanding of the establishment of a protected intracellular niche within the tissue and the host-pathogen landscape at infection bottlenecks during early stages of infection. Studying cellular host-pathogen interactions in vivo can improve our knowledge of the trajectory of infection between the initial inoculation with a dose of pathogens and the appearance of symptoms of disease.