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As most human pathogenic filariae contain <jats:italic>Wolbachia<\/jats:italic> endobacteria that synthesize the MDP-containing cell wall precursor lipid II, NOD2\u2019s role during infection with the rodent filaria <jats:italic>Litomosoides sigmodontis<\/jats:italic> was investigated. In NF\u03baB reporter-cells, worm-extract containing <jats:italic>Wolbachia<\/jats:italic> induced NOD2 and NOD1. NOD2-deficient mice infected with <jats:italic>L. sigmodontis<\/jats:italic> had significantly more worms than wildtype controls early in infection. Increased worm burden was not observed after subcutaneous infection, suggesting that protective NOD2-dependent immune responses occur within the skin. Flow cytometry demonstrated that neutrophil recruitment to the skin was impaired in NOD2<jats:sup>\u2212\/\u2212<\/jats:sup> mice after intradermal injection of third stage larvae (L3), and blood neutrophil numbers were reduced after <jats:italic>L. sigmodontis<\/jats:italic> infection. PCR array supported the requirement of NOD2 for recruitment of neutrophils to the skin, as genes associated with neutrophil recruitment and activation were downregulated in NOD2<jats:sup>\u2212\/\u2212<\/jats:sup> mice after intradermal L3 injection. Neutrophil depletion before <jats:italic>L. sigmodontis<\/jats:italic> infection increased worm recovery in wildtype mice, confirming that neutrophils are essential against invading L3 larvae. This study indicates that NOD-like receptors are implemented in first-line protective immune responses against filarial nematodes.<\/jats:p>","DOI":"10.1038\/srep39648","type":"journal-article","created":{"date-parts":[[2016,12,22]],"date-time":"2016-12-22T11:42:36Z","timestamp":1482406956000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["NOD2 dependent neutrophil recruitment is required for early protective immune responses against infectious Litomosoides sigmodontis L3 larvae"],"prefix":"10.1038","volume":"6","author":[{"given":"Jesuthas","family":"Ajendra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Specht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Ziewer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Schiefer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Pfarr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijo","family":"Par\u010dina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Kufer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Hoerauf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc P.","family":"H\u00fcbner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,22]]},"reference":[{"key":"BFsrep39648_CR1","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.coi.2008.06.001","volume":"20","author":"MH Shaw","year":"2008","unstructured":"Shaw, M. 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