i would like to follow this post too. I am also looking in to this pathway. Thanks for raising this question online

Md Shadab wrote:

> I would be happy if any one can join me in discussing

> how this parasite avert the macrophages effector function

> and persists in it till dissemination to other cell.

I'm not a medic but have a big science news link collection.

http://www.eurekalert.org/pub_releases/2009-08/icl-ppi082009.php

http://scienceblog.com/4283/t-cells-memory-may-offer-long-term-immunity-to-leishmaniasis/

http://www.eurekalert.org/pub_releases/2010-03/plos-rsl030810.php

http://www.eurekalert.org/pub_releases/2007-06/wtsi-ppf061407.php

http://www.eurekalert.org/pub_releases/2009-10/muhc-mdo100609.php

http://www.eurekalert.org/pub_releases/2010-01/asfb-sht011510.php

http://www.innovations-report.de/html/berichte/medizin_gesundheit/bericht-109475.html

http://www.innovations-report.de/html/berichte/medizin_gesundheit/bericht-102062.html

http://www.eurekalert.org/pub_releases/2009-10/muhc-mdo100609.php

http://www.eurekalert.org/pub_releases/2009-10/i-nii102309.php

http://www.eurekalert.org/pub_releases/2010-04/stri-sfb040610.php

http://news.wustl.edu/news/Pages/20920.aspx

http://www.eurekalert.org/pub_releases/2007-10/babs-nst100107.php

http://www.sciencedaily.com/releases/2007/10/071002213459.htm

http://www.physorg.com/news/2011-08-sandfly-saliva-important-clues-leishmaniasis.html

http://www.eurekalert.org/pub_releases/2011-10/wtsi-dpt102711.php

http://www.agenciasinc.es/Noticias/Un-peptido-antimicrobiano-de-la-saliva-humana-puede-matar-al-parasito-de-la-leishmaniasis

http://www.brightsurf.com/news/headlines/35543/Improved_diagnosis_of_cutaneous_leishmaniasis_thanks_to_new_techniques.html

http://www.eurekalert.org/pub_releases/2006-04/acs-pvd041906.php

http://www.physorg.com/news/2011-02-therapy-treatment-parasitic-skin-disease.html

Regards,

Joachim

Dear Joachim Pimiskern Its nice to get reply from you. The information carried in these links are wonderful. I do appreciate your cooperation in future.

Possibly one of the mechanisms by which Leishmania overcome the Macrophage like the ' Trojan Horse' in Roman history,

is IL10 induction which has oposing actions to the inflammatory mediators like TNF IL6 IL17 and IFN gamma. The trials of IL10 in Sepsis in the 90s were a follow up of this observation even though IL10 did not make any dramatic come back in the management of Sepsis. This is not the complete story and there may be other pathways by which Leishmania overcome the pattern recognition receptors(PRRs) like endosomal Toll like receptors, cytoplasmic NLRs, RIG-1 and other nucleic acid sensing mechanisms of cells like Macrophages.

Does Leishmania activate TLRs?

Yes, this parasite modulates TLR dependent production of pro and anti inflammatory mediators like IFN gama, IL-12, TGF beta, IL-10, NO.

which TLR does it trigger? since this parasite makes macrophage silent, there are also evidences and people who do not believe they really play significant TLR induced inflammasome mechanisms...Please send me some links of articles you have for example..Thanks

You can go through this paper. The concept is if we any how deplete TLR and then look into the activation of macrophage in response to the parasite, we can infer how this receptors are involved io mediating such response.

J. F. Flandin, F. Chano, and A. Descoteaux, “RNA interference reveals a role for TLR2 and TLR3 in the recognition of Leishmania donovani promastigotes by interferon-γ-primed macrophages,” European Journal of Immunology, vol. 36, no. 2, pp. 411–420, 2006. Hope it will help.

There is one more article for you to have a cmprehensive idea for macrophage TLR activation by Leishmania.

Toll-Like Receptors and Leishmaniasi

Felipe F. Tuon, Valdir S. Amato, Hélio A. Bacha, Tariq AlMusawi, Maria I. Duarte and Vicente Amato Neto

Infect. Immun. 2008, 76(3):866. DOI: 10.1128/IAI.01090-07

Can any body explain that although the parasite L . donovani evades activation of the three MAPKs (P38, ERK1/2, JNK1/2) in naive BMM , it has shown production of IL-10 in naive macrophage from peritoneum. The work is done in vitro. Second query is wheather the intact parasite do really interact with the TLRs present on macrophage's surface as siRNA against some TLRS has reported that the response as earlier observed was not the same when the particular TLRs were knocked down.

The Leishmania complex parasites primes the various intracellular signals , the important one is TLR activation ,that downstream the signal cascade for various inflamatory molecules.In classical way The TLR activation induces various downstraming signals ,strats from activation of effector molecules and Proinflamatory cytokines, irrespective NF kb too.

The entry mechanism of intracellular life style was defined, that is leishmania parasites resides in phagolysosomal vacuole ,by altering its PH, and also induces ion transport mechanism for metabolic iron acquisition respectively.

The innate mechanism of Macrophage (Peripheral derived or Bonemarrow derived) showed limited TLR priming, which means the the constant priming is disciplinary.

As per my knowledge with TLR the specificity towards leishmania Parasite is flagella or glyco proteins.So the interaction probably does not strong to change structural modification of TLR(Even though observed-might be limited).

But the recent advances in pathology and immune research , revealed the CD200 plays major role in the innate immunity to progress the infection.

CD200-an immuno inhibitary ligand that controls the INOS expression, and alters the nitrous oxide production, the dicreased CD200 expression showed decrease in gas production and favours intracellular life of Leishmania parasite.

The knock out of CD 200 showed increased level of inos (Nitrous oxide) production.

In Cell system it is considered TLR4 activation down streams the INOS expression inlarge towards innatemechanism of killing.

The data of research was saying that, the crucial step of innate mechanism escape results the pathology and ofcourse with strain genetics too.

I donot have idea on TLR may act like siRNA for other TLRs.

But this is irrespective idea, when we think fundamentally (Gene silencing technique).

Moreorless the global gene expression studies would solve some questions upon innate mechanism, perhaps involvement miRNA for proinflamatory cytokines.

The fundamental questions also raised WHY? Infamasome complex would not generate ..adapters ...subsequently caspase activities(cell death)..pro IL1b and chops.

Hope this will helpful to your ideas, and requirements, i will be happy to discus about Leishmania and its metabolism in host cell ,interactions.