Plasmodium yoeliiblood-stage primes macrophage-mediated innate immune response through modulation of toll-like receptor signalling

Fu Yong, Ding Yan, Zhou Taoli, Fu Xiaolan, Xu, Xu Wenyue

Description

Toll-like receptors (TLRs) signalling is reported to be primed by the infection of human malaria parasite, Plasmodium falciparum . However, little is known about the regulation of macrophages TLR signalling by the infection of lethal or non-lethal strain of rodent malaria parasites. Methods BALB/c mice were infected with non-lethal strain Plasmodium yoelii 17XNL or lethal strain P. yoelii 17XL. Peritoneal macrophages were isolated to study its immune response to pRBC lysate, and TLRs (TLR2, TLR4, and TLR9) agonists, and the expression of TLRs and intracellular signalling molecules were also investigated by flow cytometry and semi-quantitive RT-PCR. Results The reactivity of peritoneal macrophages from the mice infected with lethal strain P. y 17XL or non-lethal strain P. y 17XNL were enhanced to pRBC lysate, and TLR2, TLR4, and TLR9 agonists at one, three and five days post-infection. Of all the tested TLRs, only TLR2 was up-regulated on peritoneal macrophages of mice infected with either strain. However, transcription of intracellular signalling molecules MyD88, IRAK-1, and TRAF-6 was significantly up-regulated in peritoneal macrophages from mice infected either with P. yoelii 17XL or P. yoelii 17XNL at one, three and five days post-infection. However, the enhanced TLRs response of macrophage from P. yoelii 17XNL-infected mice persisted for a much longer time than that from P. yoelii 17XL-infected mice. Conclusion Both P. yoelii 17XL and 17XNL strains could enhance the response of peritoneal macrophages to pRBC lysate and TLR agonists, through up-regulating the expression of TLR2 and intracellular signalling molecules MyD88, IRAK-1, and TRAF-6. In addition, prolonged high response of macrophage from P. yoelii 17XNL-infected mice might be associated with the more efficiently controlling of P. yoelii 17XNL growth in mice at early stage.

Sujets

• Plasmodium yoelii
• Macrophage
• Toll-like receptor

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 8
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Fuet al.Malaria Journal2012,11:104 http://www.malariajournal.com/content/11/1/104

R E S E A R C H

Open Access

Plasmodium yoeliibloodstage primes macrophagemediated innate immune response through modulation of tolllike receptor signalling 1 1 1 2 1* Yong Fu , Yan Ding , Taoli Zhou , Xiaolan Fu and Wenyue Xu

Abstract Background:Tolllike receptors (TLRs) signalling is reported to be primed by the infection of human malaria parasite,Plasmodium falciparum. However, little is known about the regulation of macrophages TLR signalling by the infection of lethal or nonlethal strain of rodent malaria parasites. Methods:BALB/c mice were infected with nonlethal strainPlasmodium yoelii17XNL or lethal strainP. yoelii17XL. Peritoneal macrophages were isolated to study its immune response to pRBC lysate, and TLRs (TLR2, TLR4, and TLR9) agonists, and the expression of TLRs and intracellular signalling molecules were also investigated by flow cytometry and semiquantitive RTPCR. Results:The reactivity of peritoneal macrophages from the mice infected with lethal strainP. y17XL or nonlethal strainP. y17XNL were enhanced to pRBC lysate, and TLR2, TLR4, and TLR9 agonists at one, three and five days postinfection. Of all the tested TLRs, only TLR2 was upregulated on peritoneal macrophages of mice infected with either strain. However, transcription of intracellular signalling molecules MyD88, IRAK1, and TRAF6 was significantly upregulated in peritoneal macrophages from mice infected either withP. yoelii17XL orP. yoelii17XNL at one, three and five days postinfection. However, the enhanced TLRs response of macrophage fromP. yoelii17XNL infected mice persisted for a much longer time than that fromP. yoelii17XLinfected mice. Conclusion:BothP. yoelii17XL and 17XNL strains could enhance the response of peritoneal macrophages to pRBC lysate and TLR agonists, through upregulating the expression of TLR2 and intracellular signalling molecules MyD88, IRAK1, and TRAF6. In addition, prolonged high response of macrophage fromP. yoelii17XNLinfected mice might be associated with the more efficiently controlling ofP. yoelii17XNL growth in mice at early stage. Keywords:Plasmodium yoelii, Macrophage, Tolllike receptors

Background Malaria remains one of the most devastating diseases worldwide, with ~40% of the population at risk, and 200300 million new cases each year, resulting in about one million deaths annually [1]. The causative agents of malaria are parasitic protozoa belonging to the genus Plasmodium. Except for the virulence of infected

* Correspondence: [e-mail] 1 Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, People’s Republic of China Full list of author information is available at the end of the article

malaria parasite, presentation of clinical malaria is mainly dependent on the balance between pro and antiinflammatory responses against these parasites. Individuals who exhibit particularly weak immune responses often lead to uncontrolled parasitaemia. Thus, understanding the regulation mechanism of the immune response brought on by infection withPlasmodium parasites will provide us with potential therapeutic approaches for treating infected individuals. Although adaptive immune effectors, such asPlasmo + diumspecific CD4 abT cells and antibody [2], are mandatory for effective clearance of parasitized red

© 2012 Fu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.