Understanding and Manipulating Immune Modulation by the Microbiome
Michael A. Fischbach, Ph.D. Associate Professor, Department of Bioengineering,
Department of Microbiology & Immunology, Stanford University
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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.