Location: Diet, Genomics and Immunology LaboratoryTitle: Immunity-dependent reduction of segmented filamentous bacteria in mice infected with the helminthic parasite Nippostrongylus brasiliensis
|FRICKE, FLORIAN - University Of Maryland|
|SONG, YANG - University Of Maryland|
|WANG, AN-JIANG - University Of Maryland|
|GRINCHUK, V - University Of Maryland|
|MONGODIN, E - University Of Maryland|
|PEI, C - University Of Maryland|
|MA, B - University Of Maryland|
|LU, N - Nanchang University, Nanchang, China|
|SHEA-DONOHUE, TEREZ - University Of Maryland|
Submitted to: Microbiome
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/11/2015
Publication Date: 9/17/2015
Citation: Fricke, F.W., Song, Y., Wang, A., Smith, A.D., Grinchuk, V., Mongodin, E., Pei, C., Ma, B., Lu, N., Urban Jr, J.F., Shea-Donohue, T. 2015. Immunity-dependent reduction of segmented filamentous bacteria in mice infected with the helminthic parasite Nippostrongylus brasiliensis. BMC Microbiome. doi: 10.1186/S40168-015-0103-8.
Interpretive Summary: Helminthic (worm) therapy, i.e. therapeutic application of parasitic intestinal nematode infection, has been proposed as a treatment for inflammatory and autoimmune diseases. Clinical studies demonstrated protective effects of helminth infection against allergies and symptom improvements in inflammatory bowel disease. Supported by extensive epidemiological data, the 'hygiene hypothesis' postulates that the lack of early childhood exposure to parasitic and other infections in industrialized countries impairs development of the immune system leading to later onset of inflammatory and autoimmune diseases. Intestinal parasitic nematodes effectively modulate the host immune system and induce local and systemic anti-inflammatory immune responses. Immune modulating capabilities have also been shown for bacteria within the intestinal microbiota, including pro- and anti-inflammatory effects. Anti-inflammatory conditions are induced by Clostridia bacteria from the human microbiota, the polysaccharide A symbiosis factor of Bacteroides fragilis bacteria, and gut bacteria-derived short-chain fatty acid fermentation products that improve mucosal barrier function. Segmented filamentous bacteria (SFB) induce pro-inflammatory responses in mice and have also been identified in humans, predominantly in infants of <3 years of age and patients with ulcerative colitis. We sought to study the relationship between worm infection and the intestinal microbiota to gain mechanistic insight into the anti-inflammatory potential of parasite infection. The rationale was that these insights could help identify new targets for anti-inflammatory therapies that do not require parasite infection. The results are encouraging to scientists and nutritionists because they show that changing the distribution of SFB bacteria in the intestine can modulate the intensity of inflammation and also help control pathogenic bacterial diseases.
Technical Abstract: Immune modulation by helminth (worm) parasites could protect the host against autoimmune diseases. We report that the parasitic nematode Nippostrongylus brasiliensis induces changes in the expression of antimicrobial peptides that are associated with marked microbial composition shifts, including reductions of segmented filamentous bacteria (SFB), a group of Gram-positive, anaerobic, spore-forming Clostridia, in ileal, jejunal, colon and fecal samples. SFB reduction correlates with decreased intestinal expression of T helper 17 (Th17) cell response markers. While infection of mice genetically deficient in the type 2 response-inducing signature cytokine IL-13 and the STAT6-activated cell signaling pathway failed to reproduce these phenotypes, administration of the type 2 response-inducing cytokine IL-25 activated a similar response in wild type mice as infection with N. brasiliensis. The reduced capacity to evoke Th17 responses resulted in increased susceptibility of N. brasiliensis-infected mice to co-infection with the bacterial pathogen Citrobacter rodentium. Our results demonstrate that helminth parasite infection alters the intestinal microbiota with SFB functioning as an immune-modulating target for a Th17-dependent anti-inflammatory mechanism.