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

Ajendra, Jesuthas, Specht, Sabine, Neumann, Anna-Lena, Gondorf, Fabian, Schmidt, David, Gentil, Katrin, Hoffmann, Wolfgang H., Taylor, Mark ORCID: https://orcid.org/0000-0003-3396-9275, Hoerauf, Achim and Hübner, Marc P. (2014) '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'. PLoS ONE, Vol 9, Issue 3, e93072.

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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.

Methodology/Principal Finding

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/Significance

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.

Item Type:	Article
Subjects:	QU Biochemistry > Cells and Genetics > QU 350 Cellular structures QW Microbiology and Immunology > Immunity by Type > QW 568 Cellular immunity. Immunologic cytotoxicity. Immunocompetence. Immunologic factors (General) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General) WH Hemic and Lymphatic Systems > Lymphatic System > WH 600 Spleen
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1371/journal.pone.0093072
Depositing User:	Lynn Roberts-Maloney
Date Deposited:	21 Apr 2015 11:12
Last Modified:	16 Sep 2019 09:01
URI:	https://archive.lstmed.ac.uk/id/eprint/5094

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