title: ST2 deficiency does not impair type 2 immune responses during chronic filarial infection but leads to an increased microfilaremia due to an impaired splenic microfilarial clearance.
abstract: BACKGROUND
  Interactions of the Th2 cytokine IL-33 with its receptor ST2 lead to amplified Type 2 immune responses. As Type 2 immune responses are known to mediate protection against helminth infections we hypothesized that the lack of ST2 would lead to an increased susceptibility to filarial infections.
  
  
  RESULTS
  ST2 deficient and immunocompetent BALB/c mice were infected with the filarial nematode Litomosoides sigmodontis. At different time points after infection mice were analyzed for worm burden and their immune responses were examined within the thoracic cavity, the site of infection, and systemically using spleen cells and plasma. Absence of ST2 led to significantly increased levels of peripheral blood microfilariae, the filarial progeny, whereas L. sigmodontis adult worm burden was not affected. Development of local and systemic Type 2 immune responses were not impaired in ST2 deficient mice after the onset of microfilaremia, but L. sigmodontis infected ST2-ko mice had significantly reduced total numbers of cells within the thoracic cavity and spleen compared to infected immunocompetent controls. Pronounced microfilaremia in ST2-ko mice did not result from an increased microfilariae release by adult female worms, but an impaired splenic clearance of microfilariae.
  
  
  CONCLUSIONS
  Our findings suggest that the absence of ST2 does not impair the establishment of adult L. sigmodontis worms, but is important for the splenic clearance of microfilariae from peripheral blood. Thus, ST2 interactions may be important for therapies that intend to block the transmission of filarial disease.
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Jesuthas
authors.initials: J
authors.lastname: Ajendra
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Specht
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Neumann
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Gondorf
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Schmidt
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Gentil
authors.affiliation: Institute of Tropical Medicine, University of Tuebingen, Tuebingen, Germany.
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Hoffmann
authors.affiliation: Filariasis Research Laboratory, Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Taylor
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Hübner
mesh_terms: D000818:Animals; D002908:Chronic Disease; D005260:Female; D005368:Filariasis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005370:Filarioidea / Q000276:immunology*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D051379:Mice; D008817:Mice, Mutant Strains; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology*; D016205:Sigmodontinae; D013154:Spleen / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology
chemical_list: C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018123:Receptors, Interleukin