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Role of murine intestinal interleukin-1 receptor 1-expressing lymphoid tissue inducer-like cells in Salmonella infection.

Chen VL, Surana NK, Duan J, Kasper DL - PLoS ONE (2013)

Bottom Line: These cells are significant producers of IL-22, and this IL-22 production depends on IL-1R1 signaling.LTi-like cells are required for defense against Salmonella enterica serovar Typhimurium.Moreover, colonic LTi-like cell numbers depend on the presence of the intestinal microbiota.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.

ABSTRACT
Interleukin (IL)-1 signaling plays a critical role in intestinal immunology. Here, we report that the major population of intestinal lamina propria lymphocytes expressing IL-1 receptor 1 (IL-1R1) is the lymphoid tissue inducer (LTi)-like cell, a type of innate lymphoid cell. These cells are significant producers of IL-22, and this IL-22 production depends on IL-1R1 signaling. LTi-like cells are required for defense against Salmonella enterica serovar Typhimurium. Moreover, colonic LTi-like cell numbers depend on the presence of the intestinal microbiota. LTi-like cells require IL-1R1 for production of protective cytokines and confer protection in infectious colitis, and their cell numbers in the colon depend upon having a microbiome.

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Depletion of intestinal LTi-like cells increases susceptibility to S. Typhimurium infection.(A) Scatter plot demonstrating depletion of colonic IL-1R1+ CD4+ Lin− LTi-like cells by injection of anti-CD4 antibodies. Number of CD4+ cells (top) and LTi-like cells (bottom) isolated from cLP of Rag1−/− C57BL/6J mice is indicated. Data shown are representative of three experiments. (B-D) Weights (normalized to starting weight) (B), survival (C), and fecal burden of S. Typhimurium (D) over time following S. Typhimurium infection in isotype control (square) and anti-CD4 (αCD4; triangle) antibody-treated mice. (E) CFUs of S. Typhimurium in the liver or spleen at time of death in isotype control- and αCD4-treated mice. (F) Histological scores for the cecum and proximal colon in isotype control- and αCD4-treated mice. *, p<0.05; **, p<0.01; NS, not significant.
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pone-0065405-g004: Depletion of intestinal LTi-like cells increases susceptibility to S. Typhimurium infection.(A) Scatter plot demonstrating depletion of colonic IL-1R1+ CD4+ Lin− LTi-like cells by injection of anti-CD4 antibodies. Number of CD4+ cells (top) and LTi-like cells (bottom) isolated from cLP of Rag1−/− C57BL/6J mice is indicated. Data shown are representative of three experiments. (B-D) Weights (normalized to starting weight) (B), survival (C), and fecal burden of S. Typhimurium (D) over time following S. Typhimurium infection in isotype control (square) and anti-CD4 (αCD4; triangle) antibody-treated mice. (E) CFUs of S. Typhimurium in the liver or spleen at time of death in isotype control- and αCD4-treated mice. (F) Histological scores for the cecum and proximal colon in isotype control- and αCD4-treated mice. *, p<0.05; **, p<0.01; NS, not significant.

Mentions: Given that IL-22 is important in protection against S. Typhimurium [29], [52] and IL-1R1+ CD4+ LTi-like cells in the intestinal LP are a significant source of innate IL-22 (Fig. 2), we hypothesized that these cells play an important role in defense against S. Typhimurium. To test this hypothesis, we depleted CD4+ LTi-like cells in Rag1−/− mice using a depleting anti-CD4 antibody, an approach similar to that of previous reports [25]. By day 0, injection of anti-CD4 antibodies depleted ∼90% of colonic IL-1R1+ CD4+ LTi-like cells relative to injection of an isotype control antibody (Fig. 4A). After orally infection with S. Typhimurium, the mice injected with an anti-CD4 antibody demonstrated accelerated weight loss (Fig. 4B) and increased mortality (Fig. 4C) compared to mice injected with an isotype control. These results clearly demonstrate that CD4+ LTi-like cells are critical for survival following S. Typhimurium infection. However, it is not clear at which step of disease pathogenesis these cells are most critical: there were no differences in stool bacterial load (Fig. 4D), bacterial dissemination to the liver or spleen (Fig. 4E), or inflammation in the cecum or proximal colon (Fig. 4F).


Role of murine intestinal interleukin-1 receptor 1-expressing lymphoid tissue inducer-like cells in Salmonella infection.

Chen VL, Surana NK, Duan J, Kasper DL - PLoS ONE (2013)

Depletion of intestinal LTi-like cells increases susceptibility to S. Typhimurium infection.(A) Scatter plot demonstrating depletion of colonic IL-1R1+ CD4+ Lin− LTi-like cells by injection of anti-CD4 antibodies. Number of CD4+ cells (top) and LTi-like cells (bottom) isolated from cLP of Rag1−/− C57BL/6J mice is indicated. Data shown are representative of three experiments. (B-D) Weights (normalized to starting weight) (B), survival (C), and fecal burden of S. Typhimurium (D) over time following S. Typhimurium infection in isotype control (square) and anti-CD4 (αCD4; triangle) antibody-treated mice. (E) CFUs of S. Typhimurium in the liver or spleen at time of death in isotype control- and αCD4-treated mice. (F) Histological scores for the cecum and proximal colon in isotype control- and αCD4-treated mice. *, p<0.05; **, p<0.01; NS, not significant.
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getmorefigures.php?uid=PMC3672157&req=5

pone-0065405-g004: Depletion of intestinal LTi-like cells increases susceptibility to S. Typhimurium infection.(A) Scatter plot demonstrating depletion of colonic IL-1R1+ CD4+ Lin− LTi-like cells by injection of anti-CD4 antibodies. Number of CD4+ cells (top) and LTi-like cells (bottom) isolated from cLP of Rag1−/− C57BL/6J mice is indicated. Data shown are representative of three experiments. (B-D) Weights (normalized to starting weight) (B), survival (C), and fecal burden of S. Typhimurium (D) over time following S. Typhimurium infection in isotype control (square) and anti-CD4 (αCD4; triangle) antibody-treated mice. (E) CFUs of S. Typhimurium in the liver or spleen at time of death in isotype control- and αCD4-treated mice. (F) Histological scores for the cecum and proximal colon in isotype control- and αCD4-treated mice. *, p<0.05; **, p<0.01; NS, not significant.
Mentions: Given that IL-22 is important in protection against S. Typhimurium [29], [52] and IL-1R1+ CD4+ LTi-like cells in the intestinal LP are a significant source of innate IL-22 (Fig. 2), we hypothesized that these cells play an important role in defense against S. Typhimurium. To test this hypothesis, we depleted CD4+ LTi-like cells in Rag1−/− mice using a depleting anti-CD4 antibody, an approach similar to that of previous reports [25]. By day 0, injection of anti-CD4 antibodies depleted ∼90% of colonic IL-1R1+ CD4+ LTi-like cells relative to injection of an isotype control antibody (Fig. 4A). After orally infection with S. Typhimurium, the mice injected with an anti-CD4 antibody demonstrated accelerated weight loss (Fig. 4B) and increased mortality (Fig. 4C) compared to mice injected with an isotype control. These results clearly demonstrate that CD4+ LTi-like cells are critical for survival following S. Typhimurium infection. However, it is not clear at which step of disease pathogenesis these cells are most critical: there were no differences in stool bacterial load (Fig. 4D), bacterial dissemination to the liver or spleen (Fig. 4E), or inflammation in the cecum or proximal colon (Fig. 4F).

Bottom Line: These cells are significant producers of IL-22, and this IL-22 production depends on IL-1R1 signaling.LTi-like cells are required for defense against Salmonella enterica serovar Typhimurium.Moreover, colonic LTi-like cell numbers depend on the presence of the intestinal microbiota.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.

ABSTRACT
Interleukin (IL)-1 signaling plays a critical role in intestinal immunology. Here, we report that the major population of intestinal lamina propria lymphocytes expressing IL-1 receptor 1 (IL-1R1) is the lymphoid tissue inducer (LTi)-like cell, a type of innate lymphoid cell. These cells are significant producers of IL-22, and this IL-22 production depends on IL-1R1 signaling. LTi-like cells are required for defense against Salmonella enterica serovar Typhimurium. Moreover, colonic LTi-like cell numbers depend on the presence of the intestinal microbiota. LTi-like cells require IL-1R1 for production of protective cytokines and confer protection in infectious colitis, and their cell numbers in the colon depend upon having a microbiome.

Show MeSH
Related in: MedlinePlus