A34 EOSINOPHILS ALTER STEADY-STATE SMALL INTESTINAL IL-1α AND IL-1β LEVELS BUT ARE NOT REQUIRED FOR THE MAINTENANCE OF IGA-SECRETING LAMINA PROPRIA-RESIDENT PLASMA CELLS, SECRETORY IGA OR SERUM IGA LEVELS

摘要

Background During homeostasis eosinophils are highly abundant in the lamina propria of the small intestine. Eosinophils have been reported to play a role in promoting barrier function in the steady state intestinal tract, and in the control of intestinal colonization by harmless or symbiotic members of the bacterial microbiota. However, the role eosinophils play during enteric infection with a bacterial pathogen is unknown. Aims Our study aims to confirm the previously reported role of eosinophils in supporting intestinal barrier function and to investigate how the absence of eosinophils affects intestinal colonization by an enteric bacterial pathogen. Methods We used wildtype BALB/c and eosinophil-deficient (dblGATA knockout) BALB/c mice that had been cohoused, or bred as littermate controls, to normalize bacterial microbiota populations between mice used for experiments. To investigate steady state barrier function in these mice we used na?ve mice to quantify levels of small intestinal IL-1α and IL-1β by cytometric bead arrays, and we used ELISAs to measure levels of immunoglobulin A (sIgA) and serum IgA. Levels of lamina propria-resident B220-IgA plasma cells were quantified using flow cytometry. To investigate the contributions of eosinophils to enteric bacterial infection, mice were orally infected with Salmonella enterica serovar Typhimurium. Salmonella burdens along the intestinal tract as well as in the liver and spleen were quantified. Results We found that levels of IL-1α and IL-1β were significantly decreased in the small intestine of naive eosinophil-deficient mice, compared to wildtype mice. In na?ve wildtype and eosinophil-deficient littermate control mice, we did not detect any differences in sIgA or serum IgA levels. Additionally, levels of IgA producing plasma cells were similar in the small intestinal lamina propria between wildtype and eosinophil-deficient mice. Following oral Salmonella infection, Salmonella burdens were similar between wildtype and eosinophil-deficient mice both 24 hours and three days post-infection. Conclusions Our data supports a role for eosinophils in modifying steady-state cytokine levels in the intestinal tract. For the first time we report data on IgA levels from littermate controls of wildtype and eosinophil-deficient mice, and contrary to previously published reports, we found that eosinophils are not critical for the maintenance of intestinal sIgA, serum IgA or lamina propria resident IgA producing plasma cells. Our data further concluded that an absence of eosinophils did not impact control of Salmonella infection.