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Leishmania major inhibits IL ‐12 in macrophages by signalling through CR 3 ( CD 11b/ CD 18) and down‐regulation of ETS ‐mediated transcription
Author(s) -
RicardoCarter C.,
Favila M.,
Polando R. E.,
Cotton R. N.,
Bogard Horner K.,
Condon D.,
Ballhorn W.,
Whitcomb J. P.,
Yadav M.,
Geister R. L.,
Schorey J. S.,
McDowell M. A.
Publication year - 2013
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1111/pim.12049
Subject(s) - biology , lipopolysaccharide , mapk/erk pathway , immune system , integrin alpha m , leishmania major , cytokine , immunology , leishmania , microbiology and biotechnology , signal transduction , parasite hosting , world wide web , computer science
Summary L eishmania major is an aetiological agent of cutaneous leishmaniasis. The parasite primarily infects immune sentinel cells, specifically macrophages and dendritic cells, in the mammalian host. Infection is receptor mediated and is known to involve parasite binding to cell surface protein complement receptor 3 ( CR 3, M ac‐1, CD 11b/ CD 18). Engagement of CR 3 by various ligands inhibits production of interleukin‐12 ( IL ‐12), the cytokine that drives antileishmanial T helper 1‐type immune responses. Likewise, L . major infection inhibits IL ‐12 production and activation of host macrophages. Our data indicate that in the absence of CR 3, L . major ‐infected bone marrow‐derived macrophages produce more IL ‐12 and nitric oxide compared with WT cells upon lipopolysaccharide ( LPS ) stimulation. We therefore investigated multiple signalling pathways by which L. major may inhibit IL ‐12 transcription through CR 3 ligation. We demonstrate that L. major infection does not elicit significant NF κB p65, MAPK , IRF ‐1 or IRF ‐8 activation in WT or CD 11b‐deficient macrophages. Furthermore, infection neither inhibits LPS ‐induced MAPK or NF κB activation nor blocks IFN ‐γ‐activated IRF ‐1 and IRF ‐8. ETS ‐mediated transcription, however, is inhibited by L . major infection independently of CR 3. Our data indicate that L . major‐ mediated inhibition of IL ‐12 occurs through CR 3 engagement; however, the mechanism of inhibition is independent of NF κB, MAPK , IRF and ETS .