Exposure to ingested airborne pollutant particulate matter increases mucosal exposure to bacteria and induces early onset of inflammation in neonatal IL-10-deficient mice.

Abstract

Epidemiological associations between early-life air pollution exposure and increased risk of inflammatory bowel diseases have been shown. Our aim was to determine if exposure to airborne particulate matter (PM(10)) during the neonatal period would alter colitis in the interleukin (IL)-10(-/-) mouse model. IL-10(-/-) pregnant dams and pups were fed chow ± PM(10) (9 μg/g) and pups were studied at 10, 14, and 20 weeks. Twenty-week-old mice were given 2% dextran sodium sulfate. Metagenomic analysis of stool was performed. Bacterial translocation was assessed by serum lipopolysaccharide and culturing bacteria from mesenteric lymph nodes and spleen. Cytokine expression was measured in gut homogenates using the MesoScale discovery platform. PM(10) was applied to CMT93 cells ± J744 macrophages, and resistance and cytokine secretion were assessed. THP-1 macrophages were incubated with Escherichia coli HB101 ± PM(10) for assessment of uptake and killing. PM(10) exposure increased colonic proinflammatory cytokines and bacterial translocation into mesenteric lymph nodes, whereas IL-17A levels were reduced in PM(10)-fed 10-week-old mice. Bifidobacterium was decreased in mice fed PM(10), whereas serum lipopolysaccharide was increased. PM(10) interfered with phagocytosis and killing in THP-1 cells. In coculture, PM(10) increased tumor necrosis factor α and fluorescein isothiocyanate-dextran flux. After dextran sodium sulfate treatment, PM10-fed mice responded with increased colonic tumor necrosis factor α and IL-1β and a larger percentage of PM(10)-fed mice had live bacteria in the mesenteric lymph nodes. Our data suggest that early exposure to pollution particulates can result in an earlier onset of intestinal disease in genetically susceptible hosts and can alter responses to gut injury in later life.