Temporal expression of chemokines dictates the hepatic inflammatory infiltrate in a murine model of schistosomiasis

Melissa Burke, Donald McManus, Grant Ramm, Mary Duke, Yuesheng Li, Malcolm Jones, Geoffrey Gobert

Research output: Contribution to journalArticleResearchpeer-review

83 Citations (Scopus)

Abstract

Schistosomiasis continues to be an important cause of parasitic morbidity and mortality world-wide. Determining the molecular mechanisms regulating the development of granulomas and fibrosis will be essential for understanding how schistosome antigens interact with the host environment. We report here the first whole genome microarray analysis of the murine liver during the progression of Schistosoma japonicum egg-induced granuloma formation and hepatic fibrosis. Our results reveal a distinct temporal relationship between the expression of chemokine subsets and the recruitment of cells to the infected liver. Genes up-regulated earlier in the response included T- and B-cell chemoattractants, reflecting the early recruitment of these cells illustrated by flow cytometry. The later phases of the response corresponded with peak recruitment of eosinophils, neutrophils, macrophages and myofibroblasts/hepatic stellate cells (HSCs) and the expression of chemokines with activity for these cells including CCL11 (eotaxin 1), members of the Monocyte-chemoattractant protein family (CCL7, CCL8, CCL12) and the Hepatic Stellate Cell/Fibrocyte chemoattractant CXCL1. Peak expression of macrophage chemoattractants (CCL6, CXCL14) and markers of alternatively activated macrophages (e.g. Retnla) during this later phase provides further evidence of a role for these cells in schistosome-induced pathology. Additionally, we demonstrate that CCL7 immunolocalises to the fibrotic...
Original languageEnglish
Pages (from-to)e598-1 - e598-13
Number of pages13
JournalPLoS Neglected Tropical Diseases
Volume4
Issue number2
DOIs
Publication statusPublished - 2010
Externally publishedYes

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