Virtual memory CD8 T cells expanded by helminth infection confer broad protection against bacterial infection

Epidemiological data and animal studies suggest that helminth infection exerts potent immunomodulatory effects that dampen host immunity against unrelated pathogens. Despite this notion, we unexpectedly discovered that prior helminth infection resulted in enhanced protection against subsequent systemic and enteric bacterial infection. A population of virtual memory CD8 T (CD8 TVM) cells underwent marked expansion upon infection with the helminth Heligmosomoides polygurusby an IL-4-regulated, antigen-independent mechanism. CD8 TVMcells disseminated to secondary lymphoid organs and established a major population of the systemic CD8 T cell pool. IL-4 production elicited by protein immunization or selective activation of natural killer T cells also results in the expansion of CD8 TVMcells. Notably, CD8 TVMcells expanded by helminth infection are sufficient to transfer innate non-cognate protection against bacteria to naïve animals. This innate non-cognate “collateral protection” mediated by CD8 TVMmight provide parasitized animals an advantage against subsequent unrelated infections, and represents a potential novel strategy for vaccination.