Abstract:
BACKGROUND:During infection with Leishmania donovani, parasite control is linked to the systemic Th1 immune response, but in infected organs (liver, spleen and bone marrow), the response differs according to the micro-environment. The pleiomorphic cytokine interleukin-33 (IL-33) exerts various roles during infection, either protective or detrimental. In this study, we explored the role of IL-33 in the outcome of Leishmania infection in the spleen. METHODS:We used several mouse models, on BALB/c and C57BL/6 (B6) backgrounds, infected with L. donovani and sacrificed at 15, 30 or 60 days after infection and characterized mRNA expression of immune markers, immune cell populations, histological response, and parasite loads. RESULTS:During infection IL-33 and ST2 mRNA increased in parallel in the spleen of wild type (wt) animals and paralleled the immunodetection of ST2+ and IL-33+ cells; their expression was twice as high in BALB/c, compared to B6 mice. Mice treated with twice-weekly injections of rIL-33 had higher splenic parasite burdens on D15 (BALB/c) or on D60 (B6). In BALB/c, IL-33 treatment led to immune exhaustion with abolition of Th1 cytokine expression (IFN-γ and IL-12) in the spleen and higher serum levels of Th2 cytokines (IL-4, IL-5 and IL-13). In B6, IL-33 treatment induced the Treg cell pathway with a dramatic increase of FoxP3 mRNA induction and expression on tissue sections. IL-33-KO mice had lower parasite loads and a higher Th1 response than their wt counterparts. CONCLUSIONS:IL-33 appears as a factor of aggravation of the disease in the spleen tissue of mice infected with L. donovani.
journal_name
Parasit Vectorsjournal_title
Parasites & vectorsauthors
Lamberet A,Rostan O,Dion S,Jan A,Guegan H,Manuel C,Samson M,Gangneux JP,Robert-Gangneux Fdoi
10.1186/s13071-020-04190-3subject
Has Abstractpub_date
2020-06-22 00:00:00pages
320issue
1issn
1756-3305pii
10.1186/s13071-020-04190-3journal_volume
13pub_type
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