A perspective on single cell behavior during infection.

The interface between immune cells and intracellular bacterial pathogens produces complex, diverse interactions. During individual encounters, highly adaptable and dynamic host cells and bacteria vary in their responses, thereby contributing to well-documented heterogeneous outcomes of infection. The challenge now is to break down the multidimensionality of these interactions into informative readouts of population physiology and predictors of responses to infection. We recently reported one approach to this challenge that couples single cell RNA-seq analysis with fluorescent markers to characterize infection phenotype. 1 We detected bacterial subpopulations that elicit profoundly different host responses to infection in the specific host cells that they infect. Here we describe how heterogeneity might be maintained in populations of host and pathogens and discuss the advantages that heterogeneity confers to bacteria during infection and to host cells for eradicating a pathogen. We propose that single cell studies will allow the unraveling of host-pathogen biology and lead to an understanding of how the sum of individual encounters leads to the infection outcome of a whole organism.