• Corpus ID: 53341622

A Novel Form of Macrophage Function Inhibition by Leishmania mexicana Infection: Involvement in Inhibition of NF-kB Translocation

  title={A Novel Form of Macrophage Function Inhibition by Leishmania mexicana Infection: Involvement in Inhibition of NF-kB Translocation},
  author={Muhannad Shweash},
Manipulation of host cell signalling pathways and pro-inflammatory proteins expression by Leishmania is critical for Leishmania's survival and resultant pathology. Therefore, the characteristics of long time exposure of promastigotes mediated signalling to the MAP kinases, COX-2, iNOS, NO production and NF-κB pathways were investigated in comparison to LPS stimulation. Promastigotes caused no effect on phosphorylation of the three MAP kinases. Unlike outcome was observed on COX-2, iNOS and NO… 

Figures from this paper

Inhibition of Lipopolysaccharide-Induced Macrophage IL-12 Production by Leishmania mexicana Amastigotes: The Role of Cysteine Peptidases and the NF-κB Signaling Pathway1

The results suggest that the amastigote-specific cysteine peptidases of L. mexicana are central to the ability of the parasite to modulate signaling via NF-κB and consequently inhibit IL-12 production.

Subversion Mechanisms by Which Leishmania Parasites Can Escape the Host Immune Response: a Signaling Point of View

Some of the signaling pathways and intermediates that are repressed in infected cells are described, including JAK/STAT, Ca2+-dependent protein kinase C (PKC) isoforms, and mitogen-activated protein kinases (especially ERK1/2), and proteasome-mediated transcription factor degradation.

NO as an effector molecule of parasite killing: modulation of its synthesis by cytokines.

Activation of NF-κB by Toxoplasma gondii correlates with increased expression of antiapoptotic genes and localization of phosphorylated IκB to the parasitophorous vacuole membrane

Results from this study suggest that activation of NF-κB plays an important role in stimulation of antiapoptotic gene expression by T. gondii, and recruitment of phosphorylated IκB to the PVM implies the presence of intrinsic factor(s) in T. Gondii that might be used to manipulate the NF-σκB signaling pathway in the host to elicit a survival response during infection.

Leishmania donovani promastigotes evade the activation of mitogen‐activated protein kinases p38, c‐Jun N‐terminal kinase, and extracellular signal‐regulated kinase‐1/2 during infection of naive macrophages

Data suggest that both p38 MAPK and ERK1/2 pathways participate in some Leishmania‐induced responses in IFN‐γ‐primed BMM, and the ability of L. donovani promastigotes to avoidMAPK and NF‐κB activation in naive macrophages may be part of the strategy evolved by this parasite to evade innate immune responses.

Leishmania spp.: nitric oxide-mediated metabolic inhibition of promastigote and axenically grown amastigote forms.

Investigation of NO activity on active and dividing populations of the mammalian stage of various Leishmania species showed that NO action led to lethal metabolic inhibition in both developmental parasite stages by, at least in part, triggering iron loss from enzyme(s) with iron-sulfur prosthetic groups, in particular aconitase.

Activation of Phosphotyrosine Phosphatase Activity Attenuates Mitogen-Activated Protein Kinase Signaling and Inhibits c-FOS and Nitric Oxide Synthase Expression in Macrophages Infected with Leishmania donovani

Findings indicate that infection with L. donovani attenuates MAP kinase signaling and c-FOS and iNOS expression in macrophages by activating cellular phosphotyrosine phosphatases, which may represent a novel mechanism of macrophage deactivation during intracellular infection.

Tissue expression of inducible nitric oxide synthase is closely associated with resistance to Leishmania major

The pronounced expression of iNOS in resistant mice is an important mechanism for the elimination of Leishmania in vivo and might be a consequence of macrophage deactivation by TGF-beta and reduced responsiveness to IFN-gamma.

Yersinia virulence factor YopJ acts as a deubiquitinase to inhibit NF-κB activation

It is shown that YopJ is a promiscuous deubiquitinating enzyme that negatively regulates signaling by removing ubiquitin moieties from critical proteins, such as TRAF2, TRAF6, and IκBα.