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

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Ajendra, Jesuthas ; Specht, Sabine ; Neumann, Anna-Lena ; Gondorf, Fabian ; Schmidt, David ; Gentil, Katrin ; Hoffmann, Wolfgang H. ; Taylor, Mark J. ; Hoerauf, Achim ; Hübner, Marc P. (2014)
  • Publisher: Public Library of Science
  • Journal: PLoS ONE, volume 9, issue 3, page e93072 (issn: 1932-6203, eissn: 1932-6203)
  • Related identifiers: pmc: PMC3963995, doi: 10.1371/journal.pone.0093072
  • Subject: Mouse Models | Animal Models | qu_350 | Research Article | Immunity to Infections | Filariasis | Infectious Diseases | Immunity | Rodents | qw_568 | wc_880 | Neglected Tropical Diseases | Immune Response | Animals | Rats | Immunology | Biology and Life Sciences | Onchocerciasis | Helminth Infections | Research and Analysis Methods | Tropical Diseases | Vertebrates | Lymphatic Filariasis | Mammals | Model Organisms | Organisms | Medicine and Health Sciences | wh_600
    mesheuropmc: parasitic diseases

Background\ud \ud 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.\ud \ud Methodology/Principal Finding\ud \ud 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.\ud \ud Conclusions/Significance\ud \ud 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.
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