T Cells Kill Bacteria Captured by Transinfection from Dendritic Cells and Confer Protection in Mice

Abstract

Dendritic cells (DCs) phagocytose, process, and present bacterial antigens to T lymphocytes to trigger adaptive immunity. In vivo, bacteria can also be found inside T lymphocytes. However, T cells are refractory to direct bacterial infection, leaving the mechanisms by which bacteria invade T cells unclear. We show that T cells take up bacteria from infected DCs by the process of transinfection, which requires direct contact between the two cells and is enhanced by antigen recognition. Prior to transfer, bacteria localize to the immunological synapse, an intimate DC/T cell contact structure that activates T cells. Strikingly, T cells efficiently eliminate the transinfecting bacteria within the first hours after infection. Transinfected T cells produced high levels of proinflammatory cytokines and were able to protect mice from bacterial challenge following adoptive transfer. Thus, T lymphocytes can capture and kill bacteria in a manner reminiscent of innate immunity.

CD81 Controls Immunity to Listeria Infection through Rac-Dependent Inhibition of Proinflammatory Mediator Release and Activation of Cytotoxic T Cells

“…The higher TNF-a and NO production potential displayed by CD81 2/2 BMDCs compared with WT BMDCs could reflect a differential bacteria internalization capacity and susceptibility to infection leading to a stronger DC activation or, alternatively, that CD81 directly modulates Listeria-induced DC activation and consequently the production of proinflammatory mediators. We first analyzed the capacity of BMDCs to internalize bacteria in vitro by the gentamicin survival assay (30,31). These experiments revealed that WT and CD81 2/2 BMDCs had a comparable susceptibility to infection, as assessed by the number of CFUs at 2 h, indicating that both genotypes internalized Listeria with a similar efficiency (Fig.…”

“…BMDCs were incubated with Listeria and assessed for the gentamicin survival assay (30,31). DCs were infected with Listeria at a multiplicity of infection (moi) of 10 for 1 h at 37˚C.…”

T Cells Capture Bacteria by Transinfection from Dendritic Cells

“…The intimate contact between APCs and lymphocytes that take place during the course of IS formation also function as a platform for exchange of part of membranes, genetic material and exosomes and can be hijacked for some viruses to infect T cells; this process is called transinfection [11][12][13] . Some pathogenic bacteria (Listeria monocytogenes, Salmonella enterica and Shigella flexneri) are able to invade T lymphocytes in vivo and modify their behaviour [14][15][16] . We have recently described that T lymphocytes are also able to capture bacteria by transinfection from previously infected dendritic cells (DCs) during the course of antigen presentation 16 .…”

“…Some pathogenic bacteria (Listeria monocytogenes, Salmonella enterica and Shigella flexneri) are able to invade T lymphocytes in vivo and modify their behaviour [14][15][16] . We have recently described that T lymphocytes are also able to capture bacteria by transinfection from previously infected dendritic cells (DCs) during the course of antigen presentation 16 . T cell bacterial capture by transinfection exceedingly more effective (1,000-4,000x) than direct infections.…”

“…Additionally, flow cytometry can be used for detecting infected cells by taking advantage of the fluorescence emitted by bacteria expressing green fluorescent protein (GFP) 16,20 . Moreover, T cell transinfection can be quantified by a more sensitive approach, the gentamicin survival assay that allows measurement of a large number of events.…”