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Interaction between Chitinase 3-like 1 (CHI3L1) and bacterial protein ChiA : a decisive step for Crohn’s disease-associated adherent and invasive E. coli to enter within human macrophages.
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International audience. Crohn’s Disease (CD)-associated adherent-invasive E. coli (AIEC) survive and replicate within macrophages. It has been recently shown that AIEC replication within macrophages is modulated by Chitinase-3-Like-1 (CHI3L1) expression. Moreover, AIEC adhere to intestinal epithelial cells (IECs) through the interaction between CHI3L1 and the AIEC protein ChiA. Whether this interaction could play a role in promoting AIEC entry into macrophages is unknown. The physical interaction between ChiA and CHI3L1 have been assessed by WB and measured by MST technology. Human cultured macrophages (THP-1) and human macrophages-derived monocytes (hMDM) were infected with the reference AIEC LF82 strain and the corresponding chiA-negative mutant (LF82∆chiA). LF82∆chiA uptake within human macrophages was reduced of 40 % and 45 % in THP-1 and hMDM, respectively, compared to LF82 (p < 0.05). They were also infected by fluorescence bacteria in order to visualise them during coinfection by cell-live or confocal imagery. Live imaging recording macrophages infection showed that LF82∆chiA had a two-fold reduced entry into hMDM (p < 0.05). LF82∆chiA colonises less of the ileal and colonic mucosa of mice. A reduction of this deleted strain in lamina propria, Peyer’s patches and mesenteric ganglions compared to the wild-type strain is expected. Anti-CHI3L1 antibodies have been used to block ChiA-CHI3L1 interaction and they significantly decreased the survival ability within macrophages of several AIEC bacteria strains isolated from CD patients including LF82 (p<0.05), demonstrating that this mechanism may be common to different AIEC strains. ChiA-CHI3L1 interaction plays a key role in the CD-associated AIEC ability to enter within macrophages.
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