AUTHOR=Imperato Jessica Nancy , Xu Daqi , Romagnoli Pablo A. , Qiu Zhijuan , Perez Pedro , Khairallah Camille , Pham Quynh-Mai , Andrusaite Anna , Bravo-Blas Alberto , Milling Simon W. F. , Lefrancois Leo , Khanna Kamal M. , Puddington Lynn , Sheridan Brian S. 

TITLE=Mucosal CD8 T Cell Responses Are Shaped by Batf3-DC After Foodborne Listeria monocytogenes Infection

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.575967

DOI=10.3389/fimmu.2020.575967

ISSN=1664-3224

ABSTRACT=<p>While immune responses have been rigorously examined after intravenous <italic>Listeria monocytogenes</italic> (<italic>Lm</italic>) infection, less is understood about its dissemination from the intestines or the induction of adaptive immunity after more physiologic models of foodborne infection. Consequently, this study focused on early events in the intestinal mucosa and draining mesenteric lymph nodes (MLN) using foodborne infection of mice with <italic>Lm</italic> modified to invade murine intestinal epithelium (InlA<sup>M</sup><italic>Lm)</italic>. InlA<sup>M</sup><italic>Lm</italic> trafficked intracellularly from the intestines to the MLN and were associated with Batf3-independent dendritic cells (DC) in the lymphatics. Consistent with this, InlA<sup>M</sup><italic>Lm</italic> initially disseminated from the gut to the MLN normally in <italic>Batf3</italic><sup>–/–</sup> mice. Activated migratory DC accumulated in the MLN by 3 days post-infection and surrounded foci of InlA<sup>M</sup><italic>Lm</italic>. At this time <italic>Batf3</italic><sup>–/–</sup> mice displayed reduced InlA<sup>M</sup><italic>Lm</italic> burdens, implicating cDC1 in maximal bacterial accumulation in the MLN. <italic>Batf3</italic><sup>–/–</sup> mice also exhibited profound defects in the induction and gut-homing of InlA<sup>M</sup><italic>Lm</italic>-specific effector CD8 T cells. Restoration of pathogen burden did not rescue antigen-specific CD8 T cell responses in <italic>Batf3</italic><sup>–/–</sup> mice, indicating a critical role for <italic>Batf3</italic> in generating anti-InlA<sup>M</sup><italic>Lm</italic> immunity following foodborne infection. Collectively, these data suggest that DC play diverse, dynamic roles in the early events following foodborne InlA<sup>M</sup><italic>Lm</italic> infection and in driving the establishment of intestinal <italic>Lm</italic>-specific effector T cells.</p>