Understanding and Manipulating Immune Modulation by the Microbiome

Many microbial species colonize animals, with some species benefiting from their hosts without causing any harm. Some of these ‘commensal’ members of the microbiome can elicit a potent T cell response from their host’s immune system upon colonization.

In this talk, Michael Fischbach will describe two recent projects by his research group that aim to characterize and manipulate anti-commensal immune responses.

In the first project, he and his colleagues explored the functional properties of colonist-induced T cells by engineering the skin bacterium Staphylococcus epidermidis to express tumor antigens anchored to secreted or cell-surface proteins. Upon colonization, the engineered S. epidermidis elicited tumor-specific T cells that circulated, infiltrated local and metastatic lesions, and exerted cytotoxic activity. Their findings show that the immune response to a colonist can be redirected against a target of therapeutic interest by expressing a target-derived antigen in a commensal.

In the second project, they colonized germ-free mice with a complex defined community (made up of more than 100 bacterial strains) and profiled T cell responses to each strain individually. They found that T cell recognition of Firmicutes bacteria was focused on a widely conserved cell-surface antigen, opening the door to new therapeutic strategies in which colonist-specific immune responses are rationally altered or redirected.