Inhibition of CD40-induced N-Ras activation reduces leishmania major infection

The Journal of Immunology : Official Journal of the American Association of Immunologists
Sushmita ChakrabortyB Saha

Abstract

Leishmania major is a parasite that resides and replicates in macrophages. We previously showed that the parasite enhanced CD40-induced Raf-MEK-ERK signaling but inhibited PI3K-MKK-p38MAPK signaling to proleishmanial effects. As Raf and PI3K have a Ras-binding domain but exert opposite effects on Leishmania infection, we examined whether Ras isoforms had differential roles in Leishmania infection. We observed that L. major enhanced N-Ras and H-Ras expression but inhibited K-Ras expression in macrophages. L. major infection enhanced N-Ras activity but inhibited H-Ras and K-Ras activity. TLR2 short hairpin RNA or anti-TLR2 or anti-lipophosphoglycan Abs reversed the L. major-altered N-Ras and K-Ras expressions. Pam3CSK4, a TLR2 ligand, enhanced N-Ras expression but reduced K-Ras expression, indicating TLR2-regulated Ras expression in L. major infection. Whereas N-Ras silencing reduced L. major infection, K-Ras and H-Ras silencing enhanced the infection both in macrophages in vitro and in C57BL/6 mice. BALB/c-derived macrophages transduced with lentivirally expressed N-Ras short hairpin RNA and pulsed with L. major-expressed MAPK10 enhanced MAPK10-specific Th1-type response. CD40-deficient mice primed with these macrophages had red...Continue Reading

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Citations

Jun 27, 2018·Journal of Cellular Biochemistry·Atahar HuseinAbdur Rub
Jul 7, 2016·Antimicrobial Agents and Chemotherapy·B Eleazar Cohen
Jul 23, 2019·IUBMB Life·Abdollah JafarzadehBhaskar Saha
Apr 5, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mukesh Kumar JhaBhaskar Saha
Jan 8, 2020·Cell Communication and Signaling : CCS·Arathi NairBhaskar Saha
Feb 5, 2021·Parasitology·Sajad RashidiPaul Nguewa
Mar 30, 2021·Frontiers in Immunology·Rafael de Freitas E Silva, Esther von Stebut
Jul 3, 2021·International Journal of Molecular Sciences·Arathi NairBhaskar Saha

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