Heterogeneity in tissue culture infection models: a source of novel host–pathogen interactions?

Tissue cultures have been successfully exploited to dissect cellular and molecular mechanisms of microbial infections. Most of the methods used in this model conclude with data describing host and pathogen ‘average’ responses. Microscopy, however, reveals that such interplay is very diverse and that both partners are composed of phenotypically heterogeneous populations. Thus, upon co-incubation in the plate assay, neither all cultured host cells are infected nor all pathogen cells inflict alterations in host physiology. Despite its obvious impact in data interpretation, the basis of this heterogeneity remains in most cases unknown. Addressing this issue is encouraging since may contribute to uncover novel interactions in the host–pathogen scenario.