Humanized hemato-lymphoid system mice, or humanized mice, became in recent years a valuable tool to study the course of infection of pathogens with human host tropism. These immunodeficient mice, which are engrafted with human immune cells, showed remarkably increased susceptibility against Staphylococcus aureus infection.

Most of the early studies employed humanized NSG (huNSG, NOD-scid IL2Rgnull) mice which are widely used in the scientific community, but show poor human myeloid cell reconstitution. Since the innate immune response plays a decisive role in the defense against S. aureus, we conducted infection experiments in next-generation humanized NSG-SGM3 mice (huSGM3, NOD-scid IL2Rgnull-3/GM/SF), which have an improved myeloid cell compartment. We could demonstrate that huSGM3 showed an even higher susceptibility than huNSG although having higher numbers of human immune cells. Importantly, when looking at individual mouse data, it became clear, that the higher the number of human immune cells the more severe the infection in these mice. This was furthermore accompanied by increased levels of human cytokines and chemokines.

Currently, we are expanding our portfolio of infection models in humanized mice in terms of infection types and pathogens with the aim to learn more about the chances and limitations of this model. Additionally, we have started to investigate the human immune cell repertoire by single-cell RNA sequencing and preliminary data indicates a wide variety of human immune cell lineages and subtypes.

Knut Ohlsen and Tobias Hertlein contributed equally to this work

Relevant publications:

Hung S et al. 2022. MRSA Infection in the Thigh Muscle Leads to Systemic Disease, Strong Inflammation, and Loss of Human Monocytes in Humanized Mice. Front Immunol. 13:892053.

Hung S et al. 2023. Next-generation humanized NSG-SGM3 mice are highly susceptible to Staphylococcus aureus infection. Front Immunol. 14:1127709.