Listeria monocytogenes inhibits Th17 responses through TLR2 signaling

SONG LIU, Medical School of Nanjing University, Jinling Hospital; Xiuwen Wu, Medical School of Nanjing University Jinling Hospital; Gefei Wang, Medical School of Nanjing University, Jinling Hospital; Guosheng Gu, Medical School of Nanjing University, Jinling Hospital; Dong Hu, Medical School of Nanjing University, Jinling Hospital; Jianan Ren, Medical School of Nanjing University, Jinling Hospital

Intestinal pathogens shape mucosal immune responses and determine clinical outcome. Listeria monocytogenes (Lm) can cause severe infection in human, named listeriosis. Immunological mechanism of host defenses against Lm has been elusive.

We hypothesize that Th17 responses anticipate in the listeriosis. Immunological details of how Th17 is regulated by Lm in intestine are investigated.

We observed the localization of Lm in small intestine lamina propria and mesenteric lymph nodes using GFP-labeled Lm. We infected IL-17A-GFP mice with Lm for 3 days, and analyzed the Th17 responses in intestine using flow cytometry. We employed TLR2-/- mice, and isolated CD11c+CD103+ dendritic cells (DCs) and CD3+CD4+ T cells from small intestine lamina propria after Lm infection, then measured Ifnb1 mRNA expression in CD103+ DCs and IL-17A production by CD4+ T cells after co-stimulation by anti-CD3 and anti-CD28 antibodies for 3 days.

Lm was detected in the small intestinal lamina propria by confocal microscopy three days after infection and thus was able to invade the small intestinal lamina propria (Fig. a,b). We found that during Lm infection, Th17 cells significantly decreased in the lamina propria of small intestine while Th17 cell numbers in MLNs remained similar to those found in healthy mice (Fig. c). In support of a direct modulation of mucosal DCs function by Lm, we found that CD103+ DCs expressed significantly higher Ifnb1 mRNA three days after Lm infection. Importantly, Lm was unable to prevent the induction of Th17 cells in Tlr2-deficient mice (Fig. d).

Listeria monocytogenes inhibits intestinal Th17 responses dependent on TLR2 signaling. Considering that Lm produces lipoprotein that is predominantly recognized by TLR2 signaling, we assume a potential interaction between lipoprotein and Th17 responses, which has not been fully explored.