Does intestinal inflammation impact the lung response to bacterial endotoxin?
Lung inflammation leading to airway hyperresponsiveness causes illnesses for more than ten percent of the population in USA. Recent research had indicated that patients with inflammatory bowel disease have higher incidence of airway hyperresponsiveness compared to the general population. We investigated this observation in mice with intestinal inflammation.
We used Rag1 mice of the C57Bl/6 background, lacking functional T and B lymphocytes to generate the model of intestinal inflammation. We reconstituted the mice with T cells from genetically compatible splenocytes and induced colitis by administration of non-steroid anti-inflammatory drug (NSAID) mixed with powdered food.
Mice developed colon transmural inflammation with massive lymphocyte infiltration and disrupted epithelium allowing a direct contact between the gut immunocytes and intestinal contents. Exposure of colitic mice to bacterial endotoxin after development of colitis intensified the lung inflammation as compared to non-colitic mice with the same treatment. Lymphocytes infiltrated the lung tissue associated with fibrosis around the bronchioles are evident in histology slides (Fig. 1).
We extracted inflammatory lymphocytes from the lamina propria of inflamed colons and transferred them to normal untreated Rag1 mice. We documented the presence of these inflammatory cells in the lungs of the reconstituted mice proving that primed migratory effector lymphocytes from the inflamed gut may home in the lungs (Fig. 2).
Pulmonary CD4+ lymphocytes from colitic mice displayed proinflammatory cytokine profile manifested by high IFN-γ inflammatory cytokine and low IL10 regulatory cytokine. They expressed high ICAM1 proinflammatory receptor and had low content of CD4+, FoxP3+ regulatory lymphocytes. CD11c+ dendritic cells bind antigens from gut-localized microbiota and had higher expression of TLR4 indicating enhanced capabilities of adaptive as well as innate responses set to respond to breathed air-born recall antigens from the environment.
Division of Gastroenterology and Hepatology, Department of Internal Medicine,
University of Iowa, Carver College of Medicine, Iowa City, IA, USA
Veterans Administration Medical Center, Iowa City, IA, USA
Recirculating Immunocompetent Cells in Colitic Mice Intensify Their Lung Response to Bacterial Endotoxin.
Metwali A, Thorne PS, Ince MN, Metwali N, Winckler S, Guan X, Beyatli S, Truscott J, Urban JF Jr, Elliott DE
Dig Dis Sci. 2018 Nov